https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Tsung-Yi+Lin 2026-09-19T07:10:47Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1290881 2011-08-24T16:47:49Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> <br /> <br /> <br /> ===Ketosynthase-acyltransferase (KS-AT)===<br /> <br /> Molecular Playground banner: KS-AT The &quot;builder&quot; and the &quot;gatekeeper&quot;.<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. ([[2hg4]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The AT domain is responsible for selecting the building blocks which become incorporated into the polyketide chain, most often in the form of malonyl-CoA derivatives. Each polyketide synthase AT is exquisitely selective for one substrate type and the DEBS ATs are selective for (S)-methylmalonyl CoA. In this way it functions as the &quot;gatekeeper&quot;, preventing erroneous building blocks from becoming incorporated into the growing chain. the methylmalonyl group is transferred by the AT to the ACP, from where it can become incorporated into the polyketide by the KS domain.<br /> <br /> The KS accepts the &quot;in-progress&quot; polyketide from its upstream module, and then catalyzes the decarboxylative condensation of ACP-bound malonyl CoA derivatives with the in-progress chain. This results in an ACP-bound β-ketothioester which is processed by any other β-carbon tailoring domains present within the module.<br /> <br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Ks-at_dimer/2'&gt;KS-AT dimer&lt;/scene&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Acyl Carrier Protein (ACP)===<br /> <br /> Molecular Playground banner: &quot;the communicator&quot;.<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) ([[2ju1]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The ACP has no known catalytic activity. However it is central to the polyketide synthesis process by acting as a workbench upon which a round of chain extension is performed, interacting with every domain present within its module, as well as the downstream module. It accepts building blocks from AT, and then the growing chain from KS. Furthermore, it presents the extended chain to any ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains present, and finally passes the chain to the downstream KS or thioesterase (TE).<br /> <br /> The heart of the ACP is the phosphopantetheine (PPant) group. An approximately 20 Å long arm which is added posttranslationally. This flexible group offers a terminal thiol through which acyl groups are bound via a thioester linkage.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Dehydratase (DH)===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase ([[3el6]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Thioesterase (TE)===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)([[1mo2]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> TE is the terminal domain in DEBS, releasing the completed polyketide from the synthase by forming a 14-membered lactone. It is able to close such a large ring by threading it into a large inner cavity which stabilizes its conformation while esterification occurs.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ==3D structures of 6-deoxyerythronolide B synthase==<br /> <br /> ''Update June 2011''<br /> <br /> [[2hg4]] – yDEBS ketosynthase-acyltransferase didomain of module 5 - yeast <br /> <br /> '''DEBS1'''<br /> <br /> [[2ju1]], [[2ju2]] – yDEBS1 acyl carrier protein domain – NMR<br /> <br /> '''DEBS2'''<br /> <br /> [[3el6]] – yDEBS2 residues 2362-2653&lt;br /&gt;<br /> [[1pzq]] – yDEBS2 C-terminal domain – NMR&lt;br /&gt;<br /> [[1pzr]] – yDEBS2 C-terminal + yDEBS3 N-terminal – NMR<br /> <br /> '''DEBS3'''<br /> <br /> [[1mo2]] – yDEBS3 thioesterase domain<br /> <br /> ==Additional Resources==<br /> For additional information, see: [[Cancer]]<br /> &lt;br /&gt;<br /> <br /> [[Category:Topic Page]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1290880 2011-08-24T16:46:09Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> <br /> <br /> <br /> ===Ketosynthase-acyltransferase (KS-AT)===<br /> <br /> Molecular Playground banner: KS-AT The &quot;builder&quot; and the &quot;gatekeeper&quot;.<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. ([[2hg4]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The AT domain is responsible for selecting the building blocks which become incorporated into the polyketide chain, most often in the form of malonyl-CoA derivatives. Each polyketide synthase AT is exquisitely selective for one substrate type and the DEBS ATs are selective for (S)-methylmalonyl CoA. In this way it functions as the &quot;gatekeeper&quot;, preventing erroneous building blocks from becoming incorporated into the growing chain. the methylmalonyl group is transferred by the AT to the ACP, from where it can become incorporated into the polyketide by the KS domain.<br /> <br /> The KS accepts the &quot;in-progress&quot; polyketide from its upstream module, and then catalyzes the decarboxylative condensation of ACP-bound malonyl CoA derivatives with the in-progress chain. This results in an ACP-bound β-ketothioester which is processed by any other β-carbon tailoring domains present within the module.<br /> <br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Ks-at_dimer/2'&gt;KS-AT dimer&lt;/scene&gt;<br /> <br /> <br /> ===Acyl Carrier Protein (ACP)===<br /> <br /> Molecular Playground banner: &quot;the communicator&quot;.<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) ([[2ju1]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The ACP has no known catalytic activity. However it is central to the polyketide synthesis process by acting as a workbench upon which a round of chain extension is performed, interacting with every domain present within its module, as well as the downstream module. It accepts building blocks from AT, and then the growing chain from KS. Furthermore, it presents the extended chain to any ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains present, and finally passes the chain to the downstream KS or thioesterase (TE).<br /> <br /> The heart of the ACP is the phosphopantetheine (PPant) group. An approximately 20 Å long arm which is added posttranslationally. This flexible group offers a terminal thiol through which acyl groups are bound via a thioester linkage.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Dehydratase (DH)===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase ([[3el6]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Thioesterase (TE)===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)([[1mo2]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> TE is the terminal domain in DEBS, releasing the completed polyketide from the synthase by forming a 14-membered lactone. It is able to close such a large ring by threading it into a large inner cavity which stabilizes its conformation while esterification occurs.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ==3D structures of 6-deoxyerythronolide B synthase==<br /> <br /> ''Update June 2011''<br /> <br /> [[2hg4]] – yDEBS ketosynthase-acyltransferase didomain of module 5 - yeast <br /> <br /> '''DEBS1'''<br /> <br /> [[2ju1]], [[2ju2]] – yDEBS1 acyl carrier protein domain – NMR<br /> <br /> '''DEBS2'''<br /> <br /> [[3el6]] – yDEBS2 residues 2362-2653&lt;br /&gt;<br /> [[1pzq]] – yDEBS2 C-terminal domain – NMR&lt;br /&gt;<br /> [[1pzr]] – yDEBS2 C-terminal + yDEBS3 N-terminal – NMR<br /> <br /> '''DEBS3'''<br /> <br /> [[1mo2]] – yDEBS3 thioesterase domain<br /> <br /> ==Additional Resources==<br /> For additional information, see: [[Cancer]]<br /> &lt;br /&gt;<br /> <br /> [[Category:Topic Page]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1290879 2011-08-24T16:43:20Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> <br /> <br /> <br /> ===Ketosynthase-acyltransferase (KS-AT)===<br /> <br /> Molecular Playground banner: KS-AT The &quot;builder&quot; and the &quot;gatekeeper&quot;.<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. ([[2hg4]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/'6-deoxyerythronolide_B_synthase_(DEBS)/Ks-at/2'&gt;<br /> <br /> The AT domain is responsible for selecting the building blocks which become incorporated into the polyketide chain, most often in the form of malonyl-CoA derivatives. Each polyketide synthase AT is exquisitely selective for one substrate type and the DEBS ATs are selective for (S)-methylmalonyl CoA. In this way it functions as the &quot;gatekeeper&quot;, preventing erroneous building blocks from becoming incorporated into the growing chain. the methylmalonyl group is transferred by the AT to the ACP, from where it can become incorporated into the polyketide by the KS domain.<br /> <br /> The KS accepts the &quot;in-progress&quot; polyketide from its upstream module, and then catalyzes the decarboxylative condensation of ACP-bound malonyl CoA derivatives with the in-progress chain. This results in an ACP-bound β-ketothioester which is processed by any other β-carbon tailoring domains present within the module.<br /> <br /> ===Acyl Carrier Protein (ACP)===<br /> <br /> Molecular Playground banner: &quot;the communicator&quot;.<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) ([[2ju1]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The ACP has no known catalytic activity. However it is central to the polyketide synthesis process by acting as a workbench upon which a round of chain extension is performed, interacting with every domain present within its module, as well as the downstream module. It accepts building blocks from AT, and then the growing chain from KS. Furthermore, it presents the extended chain to any ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains present, and finally passes the chain to the downstream KS or thioesterase (TE).<br /> <br /> The heart of the ACP is the phosphopantetheine (PPant) group. An approximately 20 Å long arm which is added posttranslationally. This flexible group offers a terminal thiol through which acyl groups are bound via a thioester linkage.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Dehydratase (DH)===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase ([[3el6]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Thioesterase (TE)===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)([[1mo2]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> TE is the terminal domain in DEBS, releasing the completed polyketide from the synthase by forming a 14-membered lactone. It is able to close such a large ring by threading it into a large inner cavity which stabilizes its conformation while esterification occurs.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ==3D structures of 6-deoxyerythronolide B synthase==<br /> <br /> ''Update June 2011''<br /> <br /> [[2hg4]] – yDEBS ketosynthase-acyltransferase didomain of module 5 - yeast <br /> <br /> '''DEBS1'''<br /> <br /> [[2ju1]], [[2ju2]] – yDEBS1 acyl carrier protein domain – NMR<br /> <br /> '''DEBS2'''<br /> <br /> [[3el6]] – yDEBS2 residues 2362-2653&lt;br /&gt;<br /> [[1pzq]] – yDEBS2 C-terminal domain – NMR&lt;br /&gt;<br /> [[1pzr]] – yDEBS2 C-terminal + yDEBS3 N-terminal – NMR<br /> <br /> '''DEBS3'''<br /> <br /> [[1mo2]] – yDEBS3 thioesterase domain<br /> <br /> ==Additional Resources==<br /> For additional information, see: [[Cancer]]<br /> &lt;br /&gt;<br /> <br /> [[Category:Topic Page]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1290878 2011-08-24T16:40:13Z

<p>Tsung-Yi Lin: /* Ketosynthase-acyltransferase (KS-AT) */</p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> <br /> <br /> <br /> ===Ketosynthase-acyltransferase (KS-AT)===<br /> <br /> Molecular Playground banner: KS-AT The &quot;builder&quot; and the &quot;gatekeeper&quot;.<br /> &lt;scene name='6-deoxyerythronolide_B_synthase_(DEBS)/Ks-at/2'&gt;TextToBeDisplayed&lt;/scene&gt;<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. ([[2hg4]])' '6-deoxyerythronolide_B_synthase_(DEBS)/Ks-at/2'&gt;<br /> <br /> The AT domain is responsible for selecting the building blocks which become incorporated into the polyketide chain, most often in the form of malonyl-CoA derivatives. Each polyketide synthase AT is exquisitely selective for one substrate type and the DEBS ATs are selective for (S)-methylmalonyl CoA. In this way it functions as the &quot;gatekeeper&quot;, preventing erroneous building blocks from becoming incorporated into the growing chain. the methylmalonyl group is transferred by the AT to the ACP, from where it can become incorporated into the polyketide by the KS domain.<br /> <br /> The KS accepts the &quot;in-progress&quot; polyketide from its upstream module, and then catalyzes the decarboxylative condensation of ACP-bound malonyl CoA derivatives with the in-progress chain. This results in an ACP-bound β-ketothioester which is processed by any other β-carbon tailoring domains present within the module.<br /> <br /> ===Acyl Carrier Protein (ACP)===<br /> <br /> Molecular Playground banner: &quot;the communicator&quot;.<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) ([[2ju1]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The ACP has no known catalytic activity. However it is central to the polyketide synthesis process by acting as a workbench upon which a round of chain extension is performed, interacting with every domain present within its module, as well as the downstream module. It accepts building blocks from AT, and then the growing chain from KS. Furthermore, it presents the extended chain to any ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains present, and finally passes the chain to the downstream KS or thioesterase (TE).<br /> <br /> The heart of the ACP is the phosphopantetheine (PPant) group. An approximately 20 Å long arm which is added posttranslationally. This flexible group offers a terminal thiol through which acyl groups are bound via a thioester linkage.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Dehydratase (DH)===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase ([[3el6]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Thioesterase (TE)===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)([[1mo2]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> TE is the terminal domain in DEBS, releasing the completed polyketide from the synthase by forming a 14-membered lactone. It is able to close such a large ring by threading it into a large inner cavity which stabilizes its conformation while esterification occurs.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ==3D structures of 6-deoxyerythronolide B synthase==<br /> <br /> ''Update June 2011''<br /> <br /> [[2hg4]] – yDEBS ketosynthase-acyltransferase didomain of module 5 - yeast <br /> <br /> '''DEBS1'''<br /> <br /> [[2ju1]], [[2ju2]] – yDEBS1 acyl carrier protein domain – NMR<br /> <br /> '''DEBS2'''<br /> <br /> [[3el6]] – yDEBS2 residues 2362-2653&lt;br /&gt;<br /> [[1pzq]] – yDEBS2 C-terminal domain – NMR&lt;br /&gt;<br /> [[1pzr]] – yDEBS2 C-terminal + yDEBS3 N-terminal – NMR<br /> <br /> '''DEBS3'''<br /> <br /> [[1mo2]] – yDEBS3 thioesterase domain<br /> <br /> ==Additional Resources==<br /> For additional information, see: [[Cancer]]<br /> &lt;br /&gt;<br /> <br /> [[Category:Topic Page]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1290874 2011-08-24T16:11:28Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> <br /> <br /> <br /> ===Ketosynthase-acyltransferase (KS-AT)===<br /> <br /> Molecular Playground banner: KS-AT The &quot;builder&quot; and the &quot;gatekeeper&quot;.<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. ([[2hg4]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The AT domain is responsible for selecting the building blocks which become incorporated into the polyketide chain, most often in the form of malonyl-CoA derivatives. Each polyketide synthase AT is exquisitely selective for one substrate type and the DEBS ATs are selective for (S)-methylmalonyl CoA. In this way it functions as the &quot;gatekeeper&quot;, preventing erroneous building blocks from becoming incorporated into the growing chain. the methylmalonyl group is transferred by the AT to the ACP, from where it can become incorporated into the polyketide by the KS domain.<br /> <br /> The KS accepts the &quot;in-progress&quot; polyketide from its upstream module, and then catalyzes the decarboxylative condensation of ACP-bound malonyl CoA derivatives with the in-progress chain. This results in an ACP-bound β-ketothioester which is processed by any other β-carbon tailoring domains present within the module.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Acyl Carrier Protein (ACP)===<br /> <br /> Molecular Playground banner: &quot;the communicator&quot;.<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) ([[2ju1]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The ACP has no known catalytic activity. However it is central to the polyketide synthesis process by acting as a workbench upon which a round of chain extension is performed, interacting with every domain present within its module, as well as the downstream module. It accepts building blocks from AT, and then the growing chain from KS. Furthermore, it presents the extended chain to any ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains present, and finally passes the chain to the downstream KS or thioesterase (TE).<br /> <br /> The heart of the ACP is the phosphopantetheine (PPant) group. An approximately 20 Å long arm which is added posttranslationally. This flexible group offers a terminal thiol through which acyl groups are bound via a thioester linkage.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Dehydratase (DH)===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase ([[3el6]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Thioesterase (TE)===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)([[1mo2]])' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> TE is the terminal domain in DEBS, releasing the completed polyketide from the synthase by forming a 14-membered lactone. It is able to close such a large ring by threading it into a large inner cavity which stabilizes its conformation while esterification occurs.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ==3D structures of 6-deoxyerythronolide B synthase==<br /> <br /> ''Update June 2011''<br /> <br /> [[2hg4]] – yDEBS ketosynthase-acyltransferase didomain of module 5 - yeast <br /> <br /> '''DEBS1'''<br /> <br /> [[2ju1]], [[2ju2]] – yDEBS1 acyl carrier protein domain – NMR<br /> <br /> '''DEBS2'''<br /> <br /> [[3el6]] – yDEBS2 residues 2362-2653&lt;br /&gt;<br /> [[1pzq]] – yDEBS2 C-terminal domain – NMR&lt;br /&gt;<br /> [[1pzr]] – yDEBS2 C-terminal + yDEBS3 N-terminal – NMR<br /> <br /> '''DEBS3'''<br /> <br /> [[1mo2]] – yDEBS3 thioesterase domain<br /> <br /> ==Additional Resources==<br /> For additional information, see: [[Cancer]]<br /> &lt;br /&gt;<br /> <br /> [[Category:Topic Page]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1146687 2010-11-18T03:42:45Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.<br /> <br /> Fall 2010: New entries are due 12/10/10. Please append the designation (new Fall 2010) to your new entries. If you want to build on a previous entry, leave the earlier one intact and make a copy that you improve and mark as new. Later we will retain the new one with a merged author list.<br /> <br /> <br /> <br /> Bhatia Lab<br /> : '''[[Molecular Playground/Alginate]]''', David Griffin<br /> <br /> [http://chamberslab.com/wp/ Chambers Lab]<br /> <br /> : '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano<br /> <br /> Forbes Lab<br /> <br /> : '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> [http://www.biochem.umass.edu/garman/index.html Garman Lab]<br /> <br /> : '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> : '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli<br /> <br /> [http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]<br /> <br /> : '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy<br /> :: Best Overall CBI Molecule 2010<br /> <br /> [http://people.chem.umass.edu/jhardy/ Hardy Lab]<br /> <br /> : '''[[Molecular Playground/Caspase-7 Dynamics]]''', Daniel Seeman<br /> <br /> : '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber<br /> <br /> : '''[[Molecular Playground/Caspase-6]]''', Elih Velazquez<br /> <br /> : '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls<br /> <br /> Hebert Lab<br /> <br /> : '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd<br /> <br /> Kaltashov Lab<br /> <br /> : '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita <br /> <br /> Knapp lab<br /> <br /> :'''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin<br /> :: Best CBI Molecule Proteopedia Page 2010<br /> <br /> : '''[[Molecular Playground/FIH]]''', Cornelius Taabazuing, Breanne Holmes, John Hangasky<br /> <br /> [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> : '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia<br /> <br /> <br /> [http://robertsgroup.ecs.umass.edu/ Roberts Lab]<br /> <br /> : '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> : '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> [http://www.umass.edu/rotellogroup/ Rotello Lab]<br /> <br /> : '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino<br /> <br /> : '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang<br /> <br /> : '''[[Molecular playground/Chymotrypsin]]''', Brad<br /> <br /> : '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell<br /> <br /> Schnarr Lab <br /> <br /> : '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso<br /> <br /> Thayumanavan Lab<br /> <br /> : '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> : '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> : '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> : '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> : '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado <br /> <br /> : '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang<br /> <br /> : ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo<br /> <br /> : '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko<br /> <br /> Thayumanavan &amp; Vachet Labs<br /> <br /> : '''[[Molecular Playground/Trypsin]]''', Gladys Murage<br /> <br /> [http://people.chem.umass.edu/thompson/index.html Thompson] &amp; [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs<br /> <br /> : '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones<br /> <br /> [http://www.chem.umass.edu/~vachet/index.html Vachet Lab]<br /> <br /> : '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto<br /> :: Best CBI Molecule Jmol scenes 2010<br /> <br /> <br /> <br /> <br /> : '''[[Molecular Playground/Sandbox myoglobin]]''', Yuping Zhou <br /> <br /> <br /> <br /> Other Molecules of interest<br /> <br /> : '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> <br /> Other Laboratories<br /> <br /> : '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]<br /> <br /> <br /> Instructions:<br /> <br /> '''Congratulations to the prize-winning CBI molecules noted above! These also provide great examples to follow. Another prize for best CBI Molecules page and/or scene will be awarded in spring 2011!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7). With your chosen Jmol scene for the Molecular Playground, specify a &quot;banner&quot;, which will be projected with the molecule on the Molecular Playground. This should be a short, one-line headline for your scene that includes the name of the molecule and what is important about the scene or the molecule. Remember to design this for the general public, including non-scientists. My example is: &quot;Molecular Playground banner: A bacterial chemotaxis receptor protein used by bacteria to &quot;smell&quot; their environment.&quot;<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Please list your lab group, with your name in parentheses. That way more than one name can be associated with a Molecular Playground page (if there are several students on the Molecular Playground page, please indicate your scene with your initials). It would be great to link the lab names to web pages too. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase&diff=1142095 2010-11-09T19:25:22Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Ks-at_dimer/2'&gt;KS-AT dimer&lt;/scene&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Acp/1'&gt;ACP-representation of cartoon and stick&lt;/scene&gt;<br /> <br /> <br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Acp-_trace_representation/1'&gt;TextToBeDisplayed&lt;/scene&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase&diff=1142088 2010-11-09T19:12:41Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Ks-at_dimer/2'&gt;KS-AT dimer&lt;/scene&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase&diff=1142083 2010-11-09T19:06:47Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Ks-at_dimer/1'&gt;KS-AT dimer&lt;/scene&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase&diff=1142080 2010-11-09T19:06:09Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> &lt;scene name='User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase/Ks-at_dimer/1'&gt;TextToBeDisplayed&lt;/scene&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox&diff=1142067 2010-11-09T18:44:58Z

<p>Tsung-Yi Lin: </p> <hr /> <div>==HIV-1 protease==<br /> <br /> '''HIV-1 Protease''' is a viral aspartic protease that responsible for maturation of [http://en.wikipedia.org/wiki/HIV human immunodeficiency virus (HIV)].<br /> <br /> HIV-1 protease cleaves an [http://en.wikipedia.org/wiki/HIV human immunodeficiency virus (HIV)] precursor proteins, such as cleaving the [http://en.wikipedia.org/wiki/HIV#Replication_cycle env protein], [http://en.wikipedia.org/wiki/Gp160 glycoprotein (GP) 160], into [http://en.wikipedia.org/wiki/Gp160#gp41 gp41] <br /> and [http://en.wikipedia.org/wiki/Gp160#gp120 gp120]. [http://en.wikipedia.org/wiki/Gp160#gp120 Gp120] protrudes from the surface of HIV and binds to CD4+ T cells and [http://en.wikipedia.org/wiki/Gp160#gp41 gp41] <br /> embedded in the outer envelope help [http://en.wikipedia.org/wiki/Gp160#gp120 gp120] bind CD4+ T cells, and they both play a role in HIV's infection of [http://en.wikipedia.org/wiki/CD4_cell CD4+ T cells]. Therefore, HIV-1 protease make the virus have the ability to infect new cells by the cleave process. In other words, HIV-1 protease is responsible for maturation of the [http://en.wikipedia.org/wiki/Virion virion] by cleaving proteins into their mature form.<br /> <br /> Because the cleave step results in infectious viral particles, Drugs called protease inhibitors can interfere with this step of the viral life cycle and further prevent HIV infection progressing. Thus, many drug designs or much pharmaceutical research conduct by understanding the structure of HIV-1 protease active site and by inhibition of its activity disrupts HIV’s ability to replicate and infect additional cells.<br /> <br /> {{STRUCTURE_1hsg | PDB=1hsg | SCENE= }}<br /> <br /> == Background ==<br /> <br /> World wide, the predominant virus is HIV-1 – associated with high number of deaths.<br /> <br /> As of January 2006, it has been estimated that AIDS has killed more than 25 million people since it was first recognized on December 1, 1981. <br /> <br /> The new viral particles cannot enter the host cell without maturation which require HIV-encoded protease.<br /> <br /> Since HIV-1 protease play a vital role for infection, it has been studied as a drug target.<br /> [[Image:Infection_process.jpg|350px]]<br /> <br /> == HIV genome and HIV-1 protease ==<br /> <br /> HIV genome contains three main genes: gag, pol, and env.<br /> * gag gene codes for structural proteins which forms the ‘body’ of the viral particle, among other proteins.<br /> * Pol gene on the other hand codes for three essential enzymes which are Reverse Transcriptase (RT), Integrase (IN) and Protease (PR), among other proteins.<br /> * env gene codes for viral envelop proteins.<br /> <br /> HIV-1 Protease acts as ‘chemical scissors’ to cleave the polyproteins into functional constituent proteins. This maturation process occurs as the virion buds from the host cell.<br /> [[Image:Genome_and_protease.jpg|center|350px|thumb|The genome products (red circle) that require protease to process.]]<br /> <br /> == HIV-1 protease structure ==<br /> '''Family and Biological unit'''<br /> <br /> *HIV-1 protease belongs to aspartic family, which also includes digestive enzyme pepsin, the lysosomal cathepsin, share common catalytic mechanism <br /> <br /> *It functions as a homodimer (two identical polypeptide chains) with only one active site.<br /> <br /> *It consists 99 amino acids, which forming 10 β-strand and 1 α-helix.<br /> [[Image:Mechanism.jpg|650px]]<br /> <br /> <br /> '''Domains in HIV-1 protease'''<br /> <br /> ''Terminal domain or dimerization domain''<br /> *Consists of the termini four-stranded beta-sheet; (residues 1-4, and 95-99 of each monomer), the turn encompassing residues 4-9, and the helix (residues 86-94 of each monomer). This domain is quite crucial in dimer formation and stabilization of an active PR.<br /> <br /> ''The core domains''<br /> *These are two; one from each monomer.<br /> *Composed of primarily four beta-strand structures; and is quite compact.<br /> *Residues 10-32 and 63-85 from each monomer make up the domain sequence<br /> *The conserved Asp25-Thr26-Gly27 catalytic triad, is situated at the interface of the core domains from the two monomers.<br /> *This domain is quite useful in dimer stabilization, as well as the catalytic site stability.<br /> *The interface between the core and terminal domains is composed primarily of small hydrophobic residues. The helix of the terminal domain packs against several beta-strands of the core domain.<br /> <br /> [[Image:Domains.png|550px]]<br /> <br /> ''The flap domains''<br /> *This domain includes a mostly solvent exposed loop (residue 33-43) preceding the beta hairpin containing the flaps (residue 44-63).<br /> *Flexible flaps enclose the active site and provide important ligand binding interactions.<br /> <br /> [[Image:Binding and catalytic site.jpg|550px]]<br /> <br /> == Structure analysis ==<br /> <br /> The concavity analysis shown below can be used to determine possible binding spots. The most likely spot shown red determined with [http://hotpatch.mbi.ucla.edu/ HotPatch]<br /> <br /> [[Image:Concavity.png|460px]]<br /> <br /> Conserved residues for this protein was analyzed with [http://consurf.tau.ac.il/index.html ConSurf]<br /> <br /> [[Image:ConSurf outptus.jpg|460px]]<br /> <br /> == Reference ==<br /> *&lt;ref name= &quot;{history}&quot;&gt; Roger J Pomerantz &amp; David L Horn, Twenty years of therapy for HIV-1 infection, Nature Medicine, 2003, 9, 867-873, &lt;/ref&gt;<br /> &lt;references/&gt;<br /> <br /> *Retroviral proteases, Ben M Dunn, Maureen M Goodenow, Alla Gustchina, and Alexander Wlodawer, Genome Biol. 2002; 3(4): reviews3006.1–reviews3006.7.<br /> <br /> *Crystal Structures of Highly Constrained Substrate and Hydrolysis Products Bound to HIV-1 Protease. Implications for the Catalytic Mechanism, Joel D. A. Tyndall, Leonard K. Pattenden, Robert C. Reid, Shu-Hong Hu, Dianne Alewood, Paul F. Alewood, Terry Walsh, David P. Fairlie and Jennifer L. Martin, Biochemistry, 2008, 47 (12), pp 3736–3744<br /> <br /> *Solution Structure of the Mature HIV-1 Protease Monomer: INSIGHT INTO THE TERTIARY FOLD AND STABILITY OF A PRECURSOR, Rieko Ishima, Dennis A. Torchia, Shannon M. Lynch, Angela M. Gronenborn, and John M. Louis, J. Biol. Chem., Vol. 278, Issue 44, 43311-43319, October 31, 2003<br /> <br /> *HIV-1 protease: mechanism and drug discovery, Ashraf Brik and Chi-Huey Wong, Org. Biomol. Chem., 2003, 1, 5 – 14<br /> <br /> http://www.niaid.nih.gov/factsheets/hivinf.htm<br /> <br /> http://www.stanford.edu/group/virus/retro/2005gongishmail/HIV.html<br /> <br /> http://en.wikipedia.org/wiki/HIV</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1090352 2010-05-28T19:54:38Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.<br /> <br /> <br /> <br /> Bhatia Lab<br /> : '''[[Molecular Playground/Alginate]]''', David Griffin<br /> <br /> [http://chamberslab.com/wp/ Chambers Lab]<br /> <br /> : '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano<br /> <br /> Forbes Lab<br /> <br /> : '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> [http://www.biochem.umass.edu/garman/index.html Garman Lab]<br /> <br /> : '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> : '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli<br /> <br /> [http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]<br /> <br /> : '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy<br /> <br /> [http://people.chem.umass.edu/jhardy/ Hardy Lab]<br /> <br /> : '''[[Molecular Playground/Caspase-7 Dynamics]]''', Daniel Seeman<br /> <br /> : '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber<br /> <br /> : '''[[Molecular Playground/Caspase-6]]''', Elih Velazquez<br /> <br /> : '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls<br /> <br /> Hebert Lab<br /> <br /> : '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd<br /> <br /> Kaltashov Lab<br /> <br /> : '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita <br /> <br /> Knapp lab<br /> <br /> :'''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin<br /> <br /> : '''[[Molecular Playground/FIH]]''', Cornelius Taabazuing, Breanne Holmes, John Hangasky<br /> <br /> [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> : '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia<br /> : '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia<br /> <br /> [http://robertsgroup.ecs.umass.edu/ Roberts Lab]<br /> <br /> : '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> : '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> [http://www.umass.edu/rotellogroup/ Rotello Lab]<br /> <br /> : '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino<br /> <br /> : '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang<br /> <br /> : '''[[Molecular playground/Chymotrypsin]]''', Brad<br /> <br /> : '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell<br /> <br /> Schnarr Lab <br /> <br /> : '''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso<br /> <br /> Thayumanavan Lab<br /> <br /> : '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> : '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> : '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> : '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> : '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado <br /> <br /> : '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang<br /> <br /> : ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo<br /> <br /> : '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko<br /> <br /> Thayumanavan &amp; Vachet Labs<br /> <br /> : '''[[Molecular Playground/Trypsin]]''', Gladys Murage<br /> <br /> [http://people.chem.umass.edu/thompson/index.html Thompson] &amp; [http://www.chem.umass.edu/~rmweis/weislab/ Weis] Labs<br /> <br /> : '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones<br /> <br /> Vachet Lab<br /> <br /> : '''[[Molecular playground/beta 2 microglobulin]]''', Nick<br /> <br /> <br /> Other UMass labs<br /> <br /> : '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]<br /> <br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7). With your chosen Jmol scene for the Molecular Playground, specify a &quot;banner&quot;, which will be projected with the molecule on the Molecular Playground. This should be a short, one-line headline for your scene that includes the name of the molecule and what is important about the scene or the molecule. Remember to design this for the general public, including non-scientists. My example is: &quot;Molecular Playground banner: A bacterial chemotaxis receptor protein used by bacteria to &quot;smell&quot; their environment.&quot;<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Please list your lab group, with your name in parentheses. That way more than one name can be associated with a Molecular Playground page (if there are several students on the Molecular Playground page, please indicate your scene with your initials). It would be great to link the lab names to web pages too. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1090351 2010-05-28T19:53:57Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> <br /> <br /> <br /> ===Ketosynthase-acyltransferase (KS-AT)===<br /> <br /> Molecular Playground banner: KS-AT The &quot;builder&quot; and the &quot;gatekeeper&quot;.<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The AT domain is responsible for selecting the building blocks which become incorporated into the polyketide chain, most often in the form of malonyl-CoA derivatives. Each polyketide synthase AT is exquisitely selective for one substrate type and the DEBS ATs are selective for (S)-methylmalonyl CoA. In this way it functions as the &quot;gatekeeper&quot;, preventing erroneous building blocks from becoming incorporated into the growing chain. the methylmalonyl group is transferred by the AT to the ACP, from where it can become incorporated into the polyketide by the KS domain.<br /> <br /> The KS accepts the &quot;in-progress&quot; polyketide from its upstream module, and then catalyzes the decarboxylative condensation of ACP-bound malonyl CoA derivatives with the in-progress chain. This results in an ACP-bound β-ketothioester which is processed by any other β-carbon tailoring domains present within the module.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Acyl Carrier Protein (ACP)===<br /> <br /> Molecular Playground banner: &quot;the communicator&quot;.<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> The ACP has no known catalytic activity. However it is central to the polyketide synthesis process by acting as a workbench upon which a round of chain extension is performed, interacting with every domain present within its module, as well as the downstream module. It accepts building blocks from AT, and then the growing chain from KS. Furthermore, it presents the extended chain to any ketoreductase (KR), dehydratase (DH), and enoyl reductase (ER) domains present, and finally passes the chain to the downstream KS or thioesterase (TE).<br /> <br /> The heart of the ACP is the phosphopantetheine (PPant) group. An approximately 20 Å long arm which is added posttranslationally. This flexible group offers a terminal thiol through which acyl groups are bound via a thioester linkage.<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Dehydratase (DH)===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===Thioesterase (TE)===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> TE is the terminal domain in DEBS, releasing the completed polyketide from the synthase by forming a 14-membered lactone. It is able to close such a large ring by threading it into a large inner cavity which stabilizes its conformation while esterification occurs.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1086719 2010-05-14T02:38:50Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the beta-position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> .<br /> <br /> <br /> ===KS-AT===<br /> <br /> Molecular Playground banner: KS-AT is responsible for one round of chain extension, &quot;the carbon adding worker&quot;.<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> Molecular Playground banner: carrying the carbon extender unit, &quot;the communicator&quot;.<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1086717 2010-05-14T02:04:33Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large and structurally diverse class of natural products produced by bacteria, fungi, and plants. They exhibit a wide variety of biological activities including antibiotic, antitumor, anticancer, among others.<br /> <br /> In Nature, polyketides are synthesized by large multifunctional proteins called polyketide synthases (PKSs).. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 domains in the N-terminal loading module, responsible for priming the synthase with a proprionate starter unit, and 26 domains in the six extender modules, Each extender module contains at least three essential domains: a ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, the AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA onto the phosphopantetheine arm of ACP. The KSdomain accepts the polyketide chain from the previous module and catalyzes chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit is added, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to yield a hydroxyl, enoyl, or methylene group at the -position. Finally, the thioesterase (TE) domain that located at the C-terminus of DEBS module 6 promotes the macrocyclization event which releases the final product, 6-dEB. <br /> .<br /> <br /> <br /> ===KS-AT===<br /> <br /> Molecular Playground banner: KS-AT is responsible for one round of chain extension, &quot;the carbon adding worker&quot;.<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> Molecular Playground banner: carrying the carbon extender unit, &quot;the communicator&quot;.<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082618 2010-05-04T07:24:01Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases (PKS). Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 catalytic domains in a loading module and 26 domains in six extender modules, and the loading module is responsible for the priming, and each extender module is responsible for one round of chain extension and possible modification on the elongating polyketide intermediate. Each extender module contains at least three essential domains: a β-keto acyl synthase or ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA metabolite onto the phosphopantethinyl arm of ACP, and KS domains take over the polyketide chain from the previous module or loading module and further catalyze the chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> Molecular Playground banner: KS-AT is responsible for one round of chain extension, &quot;the carbon adding worker&quot;.<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> Molecular Playground banner: carrying the carbon extender unit, &quot;the communicator&quot;.<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082617 2010-05-04T07:23:14Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases (PKS). Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large subunits, DEBS1, DEBS2 and DEBS3, each containing two modules and above 300 kD in size. There are 2 catalytic domains in a loading module and 26 domains in six extender modules, and the loading module is responsible for the priming, and each extender module is responsible for one round of chain extension and possible modification on the elongating polyketide intermediate. Each extender module contains at least three essential domains: a β-keto acyl synthase or ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). In detail, AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA metabolite onto the phosphopantethinyl arm of ACP, and KS domains take over the polyketide chain from the previous module or loading module and further catalyze the chain elongation reaction by adding an ACP-bound extender unit through decarboxylative condensation.<br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> Molecular Playground banner: KS-AT is responsible for one round of chain extension, &quot;the carbon adding worker&quot;.<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> Molecular Playground banner: carrying the carbon extender unit, &quot;the communicator&quot;.<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1082063 2010-04-30T16:31:42Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Schnarr lab (Tsung-Yi Lin)<br /> <br /> '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III<br /> <br /> '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)<br /> <br /> '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd<br /> <br /> '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia<br /> <br /> '''[[Human PPCA|Molecular Playground/Human PPCA]]''', Nilima Kolli<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1082061 2010-04-30T16:30:35Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Schnarr lab (Tsung-Yi Lin)<br /> <br /> '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III<br /> <br /> '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)<br /> <br /> '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd<br /> <br /> '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia<br /> <br /> '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082058 2010-04-30T16:27:11Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases (PKS). Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each above 300 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module contains at least three essential domains; a β-keto acyl synthase or ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding onto the growing polyketide chain. In detail, AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes an ACP-bound extender unit adding onto the elongating polyketide chain from the previous module or loading module by decarboxylative condensation.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> Molecular Playground banner: KS-AT is responsible for one round of chain extension, &quot;the carbon adding worker&quot;.<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> Molecular Playground banner: carrying the carbon extender unit, &quot;the communicator&quot;.<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> Molecular Playground banner: make modification on beta-keto-acyl-ACP, &quot;the decorator&quot;.<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> Molecular Playground banner: cyclize the molecule, &quot;the closer&quot;. <br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082052 2010-04-30T16:17:45Z

<p>Tsung-Yi Lin: </p> <hr /> <div>One of the '''[[CBI Molecules]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases (PKS). Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each above 300 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module contains at least three essential domains; a β-keto acyl synthase or ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding onto the growing polyketide chain. In detail, AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes an ACP-bound extender unit adding onto the elongating polyketide chain from the previous module or loading module by decarboxylative condensation.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082051 2010-04-30T16:16:51Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A '''[[CBI Molecule]]''' being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases (PKS). Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each above 300 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module contains at least three essential domains; a β-keto acyl synthase or ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding onto the growing polyketide chain. In detail, AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes an ACP-bound extender unit adding onto the elongating polyketide chain from the previous module or loading module by decarboxylative condensation.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082050 2010-04-30T16:14:09Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases (PKS). Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each above 300 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module contains at least three essential domains; a β-keto acyl synthase or ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding onto the growing polyketide chain. In detail, AT domain selects the appropriate carbon extender unit and transfers the units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes an ACP-bound extender unit adding onto the elongating polyketide chain from the previous module or loading module by decarboxylative condensation.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1082012 2010-04-30T14:51:39Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Schnarr lab (Tsung-Yi Lin)<br /> <br /> '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III<br /> <br /> '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)<br /> <br /> '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> [http://proteopedia.org/wiki/index.php/Molecular_Playground/ERMan1], Johan Sunryd<br /> <br /> '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1082011 2010-04-30T14:41:53Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Schnarr lab(Tsung-Yi Lin)<br /> <br /> '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III<br /> <br /> '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)<br /> <br /> '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> [http://proteopedia.org/wiki/index.php/Molecular_Playground/ERMan1], Johan Sunryd<br /> <br /> '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1082010 2010-04-30T14:41:13Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[6-deoxyerythronolide B synthase (DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin<br /> <br /> '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III<br /> <br /> '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)<br /> <br /> '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> [http://proteopedia.org/wiki/index.php/Molecular_Playground/ERMan1], Johan Sunryd<br /> <br /> '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1082009 2010-04-30T14:40:35Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin<br /> <br /> '''[[Molecular Playground/Lysozime ]]''', Daniella Gonzalez<br /> <br /> '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> <br /> '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> '''[[Molecular Playground/Taxol]]''', Rohan Patil<br /> <br /> '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> <br /> '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III<br /> <br /> '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Rotello lab (Daniel Moyano-Marino)<br /> <br /> '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> <br /> '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> <br /> [http://proteopedia.org/wiki/index.php/Molecular_Playground/ERMan1], Johan Sunryd<br /> <br /> '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=6-deoxyerythronolide_B_synthase_(DEBS)&diff=1082008 2010-04-30T14:36:50Z

<p>Tsung-Yi Lin: New page: A CBI Molecule being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://...</p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin&diff=1082007 2010-04-30T14:36:06Z

<p>Tsung-Yi Lin: </p> <hr /> <div>Chemistry graduate student at UMass, Amherst.<br /> <br /> *[[User:Tsung-Yi Lin/Sandbox]]<br /> <br /> *[[User:Tsung-Yi Lin/Sandbox 1]]<br /> <br /> *[[User:Tsung-Yi Lin/6-deoxyerythronolide B synthase]]<br /> <br /> *[[6-deoxyerythronolide B synthase (DEBS)]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1079341 2010-04-22T18:21:53Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> <br /> '''[[User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase]]''', Tsung-Yi Lin<br /> <br /> <br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=CBI_Molecules&diff=1079340 2010-04-22T18:20:39Z

<p>Tsung-Yi Lin: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground]. Follow the links below to read nontechnical descriptions in Proteopedia.<br /> <br /> UMass CBI Members, add your molecules to the list; follow the instructions below the list.<br /> <br /> <br /> '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Thompson &amp; Weis laboratories<br /> '''[[User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase]]''', Tsung-Yi Lin<br /> <br /> Instructions:<br /> <br /> '''We plan to award a prize for the best CBI Molecules page and/or scene!'''<br /> <br /> Choose a molecule that is part of your research project.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. If you are new to Proteopedia, click Help in the navigation box on the left to get started.<br /> <br /> 2. Make yourself a sandbox page in which you will develop your CBI Molecule scene and description (Enter &quot;User:your name/sandbox 1&quot; (omit quotes) in the search box, then follow instructions to edit this page. See example [[User:Lynmarie K Thompson/Sandbox 1]]). <br /> <br /> 3. Follow the format of the sample CBI molecule page [[Molecular Playground/Bacterial Chemotaxis Receptors]]. Easiest way to do this is to copy this page (in editing mode), paste it into your sandbox page, keep the first paragraph about CBI molecules, and then edit to describe and display your molecule. Your goal is to make this an interesting, nontechnical description of the molecule. If multiple people in one group work on the same molecule, you can each make different scenes for the same CBI molecule and each describe them on the same proteopedia page. Talk with each other about your plans so you are not duplicating efforts.<br /> <br /> 4. Create an attractive scene for your molecule: use the scene authoring tools in the edit mode to create the view you like, then copy the wiki text into your window.<br /> <br /> 5. Follow instructions at [[Molecular Playground/Procedures]] as well. But don't &quot;capture the state script for your scene&quot;; that will be done for you (see #7).<br /> <br /> 6. When you are happy with your sandbox page, make yourself a permanent Proteopedia page, which will be editable by others. Enter &quot;Molecular Playground/your molecule&quot; (omit quotes) in the search box, then follow the instructions to create a new page with this title. Copy the content of your sandbox to this new page.<br /> <br /> 7. When you have finished the final version of your page and scene, edit this CBI Molecules page to add a listing and link for your molecule, following the &quot;Bacterial chemotaxis receptors&quot; example above. Once this link is there, your scene is considered done, and someone will capture the state script for display on the Molecular Playground.</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase&diff=1079339 2010-04-22T18:19:29Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/6-deoxyerythronolide B synthase/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/6-deoxyerythronolide_B_synthase&diff=1079338 2010-04-22T18:18:07Z

<p>Tsung-Yi Lin: New page: A CBI Molecule being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://...</p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin&diff=1079337 2010-04-22T18:17:45Z

<p>Tsung-Yi Lin: </p> <hr /> <div>Chemistry graduate student at UMass, Amherst.<br /> <br /> *[[User:Tsung-Yi Lin/Sandbox]]<br /> <br /> *[[User:Tsung-Yi Lin/Sandbox 1]]<br /> <br /> *[[User:Tsung-Yi Lin/6-deoxyerythronolide B synthase]]</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077430 2010-04-21T00:09:31Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)|left|300px]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077429 2010-04-21T00:08:04Z

<p>Tsung-Yi Lin: </p> <hr /> <div>A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077428 2010-04-21T00:04:16Z

<p>Tsung-Yi Lin: </p> <hr /> <div><br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077427 2010-04-21T00:02:58Z

<p>Tsung-Yi Lin: </p> <hr /> <div><br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB) (Fig. 2), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> [[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)]]<br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077426 2010-04-21T00:02:24Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:DEBS.png|frame|6-deoxyerythronolide B synthase (DEBS)]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB) (Fig. 2), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=File:DEBS.png&diff=1077425 2010-04-21T00:01:15Z

<p>Tsung-Yi Lin: </p> <hr /> <div>== Licensing ==<br /> {{subst:Permission from license selector}}</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077424 2010-04-20T23:55:11Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> <br /> Polyketides are a large class of natural products produced by bacteria, fungi, and plants. Polyketides exhibit diverse structures and a wide variety of biological activities, which includes antibiotic, antitumor, anticancer, and other biological properties.<br /> <br /> In nature, polyketides are synthesized by large multifunctional enzymes called polyketide synthases. Among several characterized PKSs, the biosynthesis of the polyketide Core of erythromycin A, 6-deoxyerythronolide B (6-dEB) (Fig. 2), has provided the paradigm for understanding the structure and function of the PKSs that are responsible for assembling complex polyketides .<br /> <br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077423 2010-04-20T23:52:13Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> The 6-deoxyerythronolide B synthase (DEBS), which catalyzes the formation of 6-dEB, consists of three large polypeptides, DEBS1, DEBS2 and DEBS3, each 330 to 370 kD in size, and each polypeptide in DEBS is composed of two modules, where a module includes all the catalytic domains responsible for one round of chain extension and modification on the growing polyketide intermediate. Each module minimally contains three essential domains; a β-keto acyl synthase, simply referred to as ketosynthase (KS), an acyl transferase (AT) and an acyl carrier protein (ACP). All of them catalyze extender units adding to the growing polyketide chain. In detail, AT domain selects the appropriate monomer unit and transfers the carbon extender units from acyl-CoA metabolite onto the phosphopantetheinyl arm of ACP, and KS domains catalyzes decarboxylative condensation between the growing polyketide chain from the previous module and an ACP-bound extender unit.<br /> <br /> After the extender unit was added onto the elongating polyketide chain, it can be further processed by optional tailoring domains, including ketoreductases (KRs), dehydratases (DHs), and enoyl reductases (ERs), to change the oxidation state of each ketide-unit and to yield a hydroxyl, enoyl, or methylene group that may be present in the final product. In addition, the thioesterase (TE) domain that located at the C-terminus of module 6 of DEBS catalyzes the macrocyclization and releases the final product 6-dEB.<br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077115 2010-04-17T03:27:48Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> <br /> <br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077114 2010-04-17T03:26:49Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077113 2010-04-17T03:25:42Z

<p>Tsung-Yi Lin: /* KS-AT */</p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;<br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/&gt;<br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077112 2010-04-17T03:24:46Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;<br /> <br /> <br /> <br /> <br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;<br /> <br /> <br /> <br /> <br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077111 2010-04-17T03:23:15Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/1'/&gt;<br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/2'/&gt;<br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/3'/&gt;<br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)' scene='User:Tsung-Yi Lin/Sandbox_1/Loadedfrompdb/4'/&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077110 2010-04-17T03:09:47Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> ===DH===<br /> <br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)'&gt;<br /> <br /> ===ACP===<br /> <br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'&gt;<br /> <br /> ===KS-AT===<br /> <br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)'&gt;<br /> ===TE===<br /> <br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)'&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077109 2010-04-17T03:09:25Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> ===DH===<br /> {{Clear}}<br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)'&gt;<br /> <br /> ===ACP===<br /> {{Clear}}<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'&gt;<br /> <br /> ===KS-AT===<br /> {{Clear}}<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)'&gt;<br /> ===TE===<br /> {{Clear}}<br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)'&gt;</div>

Tsung-Yi Lin https://proteopedia.org/index.php?title=User:Tsung-Yi_Lin/Sandbox_1&diff=1077108 2010-04-17T03:08:07Z

<p>Tsung-Yi Lin: </p> <hr /> <div>[[Image:intactModelLargeText.jpg|frame|Bacterial chemotaxis receptor]]<br /> <br /> A [[CBI Molecule]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].<br /> <br /> Many bacteria can &quot;smell&quot; their surroundings and &quot;choose&quot; where to go. They detect molecules such as amino acids or sugars using receptors that bind these molecules and transmit a signal into the cell. This signal controls several proteins which ultimately control the direction of rotation of the motors that rotate the flagella. One direction causes the cell to continue swimming; the other direction causes the cell to tumble. When an attractant molecule binds, the receptor signals: &quot;Things look good, keep swimming!&quot; The opposite signal occurs when bacteria sense a repellant or less attractant molecules: &quot;Time to tumble and try a new swimming direction.&quot;<br /> <br /> <br /> A bacterial chemotaxis receptor is an unusually long alpha-helical structure. The attractant molecule (the ligand) binds near the top of this picture and sends a signal across the membrane into the cell to control proteins that bind near the bottom. This is a model of the structure of the receptor based on experimental structures of pieces of related proteins.<br /> <br /> {{Clear}}<br /> &lt;applet load='3EL6' size='[450,338]' frame='true' align='right'<br /> caption='Crystal Structure of the Erythromycin Dehydratase (3EL6)'&gt;<br /> <br /> <br /> {{Clear}}<br /> &lt;applet load='2JU1' size='[450,338]' frame='true' align='right'<br /> caption='Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS) (2JU1)'&gt;<br /> <br /> <br /> {{Clear}}<br /> &lt;applet load='2HG4' size='[450,338]' frame='true' align='right'<br /> caption='Structure of the ketosynthase-acyltransferase didomain of module 5 from DEBS. (2HG4)'&gt;<br /> <br /> {{Clear}}<br /> &lt;applet load='1MO2' size='[450,338]' frame='true' align='right'<br /> caption='Thioesterase Domain from 6-Deoxyerythronolide Synthase (DEBS TE)(1MO2)'&gt;</div>

Tsung-Yi Lin