Sandbox Reserved 918: Difference between revisions

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===Binding Pocket===

The specificity of the DPP IV in its ability to discern the proline from other amino acids can be seen in the binding pocket where two glutamates, <scene name='57/573132/1x70_glutamates/3'>Glu205-Glu206</scene> orient the substrate allowing only small residues like proline or alanine to fit. The [http://en.wikipedia.org/wiki/Glutamic_acid glutamates] form a [http://en.wikipedia.org/wiki/Salt_bridge_(protein_and_supramolecular) salt bridge] with the N-terminus, positioning the substrate so that only two amino acids can fit into position for ~~hydrolyses~~. <ref name="Gorrell">PMID: 15584901</ref> Examples of DPP IV substrates with alanine or proline at their N-terminus are:

The specificity of the DPP IV in its ability to discern the proline from other amino acids can be seen in the binding pocket where two glutamates, <scene name='57/573132/1x70_glutamates/3'>Glu205-Glu206</scene> orient the substrate allowing only small residues like proline or alanine to fit. The [http://en.wikipedia.org/wiki/Glutamic_acid glutamates] form a [http://en.wikipedia.org/wiki/Salt_bridge_(protein_and_supramolecular) salt bridge] with the N-terminus, positioning the substrate so that only two amino acids can fit into position for hydrolysis. <ref name="Gorrell">PMID: 15584901</ref> Examples of DPP IV substrates with alanine or proline at their N-terminus are:

{| class="wikitable" style="text-align:center; width:550px; height:200px;"

|+

Line 42:

===Active Site===

These substrates, along with many others, are cleaved by DPP IV at its active site containing a [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] composed of <scene name='57/573132/1x70_catalytictriad/1'>Ser630, His740, and Asp708</scene>. The substrate shown is a DPP IV ~~inhibitorThis~~ Serine-~~Histadine~~-Asparatate motif, best known in the enzyme [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin], uses acid-base chemistry to facilitate the binding, cleaving, and release of the given substrate. The mechanism of the reaction is as follows:

These substrates, along with many others, are cleaved by DPP IV at its active site containing a [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] composed of <scene name='57/573132/1x70_catalytictriad/1'>Ser630, His740, and Asp708</scene>. The substrate shown is a DPP IV inhibitor. This Serine-Histidine-Asparatate motif, best known in the enzyme [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin], uses acid-base chemistry to facilitate the binding, cleaving, and release of the given substrate. The mechanism of the reaction is as follows:

# Substrate binds to enzyme and carbonyl carbon is positioned by [http://en.wikipedia.org/wiki/Active_site active site].

# ~~Histadine~~, via hydrogen bond with asparatate, becomes more [http://en.wikipedia.org/wiki/Electronegativity electronegative] and therefore readily accepts the hydrogen from the -OH group on serine, making it [http://en.wikipedia.org/wiki/Nucleophile nucleophilic]. [[Image:Serine_protease_mechanism_by_snellios.png|right|thumb|150px|<font size=".8"><div style="text-align: center;"> Arrow Pushing Mechanism </div></font>]]

# Histidine, via hydrogen bond with asparatate, becomes more [http://en.wikipedia.org/wiki/Electronegativity electronegative] and therefore readily accepts the hydrogen from the -OH group on serine, making it [http://en.wikipedia.org/wiki/Nucleophile nucleophilic]. [[Image:Serine_protease_mechanism_by_snellios.png|right|thumb|150px|<font size=".8"><div style="text-align: center;"> Arrow Pushing Mechanism </div></font>]]

# The nucleophilic serine attacks the [http://en.wikipedia.org/wiki/Carbonyl carbonyl] carbon, generating a [http://goldbook.iupac.org/T06289.html tetrahedral intermediate] (as seen in the [http://en.wikipedia.org/wiki/Arrow_pushing arrow pushing mechanism]).

# The peptide bond is cleaved and the electrons from it move to attack the hydrogen on the ~~histadine~~. This half of the substrate now dissociates, leaving the other half still bound to serine.

# The peptide bond is cleaved and the electrons from it move to attack the hydrogen on the histidine. This half of the substrate now dissociates, leaving the other half still bound to serine.

# ~~Histadine~~ then deprotonates a water molecule, forming a nucleophilic [http://en.wikipedia.org/wiki/Hydroxide hydroxide group] that attacks the serine-bound carbonyl carbon.

# Histidine then deprotonates a water molecule, forming a nucleophilic [http://en.wikipedia.org/wiki/Hydroxide hydroxide group] that attacks the serine-bound carbonyl carbon.

# As the electrons move from the oxygen back down to reform the double bond, serine [http://en.wikipedia.org/wiki/Dissociation_(chemistry) dissociates] as a leaving group and the other half of the substrate dissociates from the enzyme.

# The negative oxygen on serine readily accepts the hydrogen from ~~histadine~~ and in doing so regenerates the active site of the enzyme.

# The negative oxygen on serine readily accepts the hydrogen from histidine and in doing so regenerates the active site of the enzyme.

</div>

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@@ Line 16: / Line 16: @@
 <StructureSection load='1X70' size='350' frame='true' align='right' caption='Biological Dimer of DPP IV' scene='57/573132/1x70_basic_dimer/1'>
 ===Binding Pocket===
-The specificity of the DPP IV in its ability to discern the proline from other amino acids can be seen in the binding pocket where two glutamates, <scene name='57/573132/1x70_glutamates/3'>Glu205-Glu206</scene> orient the substrate allowing only small residues like proline or alanine to fit. The [http://en.wikipedia.org/wiki/Glutamic_acid glutamates] form a [http://en.wikipedia.org/wiki/Salt_bridge_(protein_and_supramolecular) salt bridge] with the N-terminus, positioning the substrate so that only two amino acids can fit into position for hydrolyses. <ref name="Gorrell">PMID: 15584901</ref> Examples of DPP IV substrates with alanine or proline at their N-terminus are:
+The specificity of the DPP IV in its ability to discern the proline from other amino acids can be seen in the binding pocket where two glutamates, <scene name='57/573132/1x70_glutamates/3'>Glu205-Glu206</scene> orient the substrate allowing only small residues like proline or alanine to fit. The [http://en.wikipedia.org/wiki/Glutamic_acid glutamates] form a [http://en.wikipedia.org/wiki/Salt_bridge_(protein_and_supramolecular) salt bridge] with the N-terminus, positioning the substrate so that only two amino acids can fit into position for hydrolysis. <ref name="Gorrell">PMID: 15584901</ref> Examples of DPP IV substrates with alanine or proline at their N-terminus are:
 {| class="wikitable" style="text-align:center; width:550px; height:200px;"
 |+
@@ Line 42: / Line 42: @@
 ===Active Site===
-These substrates, along with many others, are cleaved by DPP IV at its active site containing a [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] composed of <scene name='57/573132/1x70_catalytictriad/1'>Ser630, His740, and Asp708</scene>. The substrate shown is a DPP IV inhibitorThis Serine-Histadine-Asparatate motif, best known in the enzyme [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin], uses acid-base chemistry to facilitate the binding, cleaving, and release of the given substrate. The mechanism of the reaction is as follows:
+These substrates, along with many others, are cleaved by DPP IV at its active site containing a [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] composed of <scene name='57/573132/1x70_catalytictriad/1'>Ser630, His740, and Asp708</scene>. The substrate shown is a DPP IV inhibitor. This Serine-Histidine-Asparatate motif, best known in the enzyme [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin], uses acid-base chemistry to facilitate the binding, cleaving, and release of the given substrate. The mechanism of the reaction is as follows:
 <div style="text-align: left;">
 # Substrate binds to enzyme and carbonyl carbon is positioned by [http://en.wikipedia.org/wiki/Active_site active site].
-# Histadine, via hydrogen bond with asparatate, becomes more [http://en.wikipedia.org/wiki/Electronegativity electronegative] and therefore readily accepts the hydrogen from the -OH group on serine, making it [http://en.wikipedia.org/wiki/Nucleophile nucleophilic]. [[Image:Serine_protease_mechanism_by_snellios.png|right|thumb|150px|<font size=".8"><div style="text-align: center;"> Arrow Pushing Mechanism  </div></font>]]
+# Histidine, via hydrogen bond with asparatate, becomes more [http://en.wikipedia.org/wiki/Electronegativity electronegative] and therefore readily accepts the hydrogen from the -OH group on serine, making it [http://en.wikipedia.org/wiki/Nucleophile nucleophilic]. [[Image:Serine_protease_mechanism_by_snellios.png|right|thumb|150px|<font size=".8"><div style="text-align: center;"> Arrow Pushing Mechanism  </div></font>]]
 # The nucleophilic serine attacks the [http://en.wikipedia.org/wiki/Carbonyl carbonyl] carbon, generating a [http://goldbook.iupac.org/T06289.html tetrahedral intermediate] (as seen in the [http://en.wikipedia.org/wiki/Arrow_pushing arrow pushing mechanism]).
-# The peptide bond is cleaved and the electrons from it move to attack the hydrogen on the histadine. This half of the substrate now dissociates, leaving the other half still bound to serine.
+# The peptide bond is cleaved and the electrons from it move to attack the hydrogen on the histidine. This half of the substrate now dissociates, leaving the other half still bound to serine.
-# Histadine then deprotonates a water molecule, forming a nucleophilic [http://en.wikipedia.org/wiki/Hydroxide hydroxide group] that attacks the serine-bound carbonyl carbon.
+# Histidine then deprotonates a water molecule, forming a nucleophilic [http://en.wikipedia.org/wiki/Hydroxide hydroxide group] that attacks the serine-bound carbonyl carbon.
 # As the electrons move from the oxygen back down to reform the double bond, serine [http://en.wikipedia.org/wiki/Dissociation_(chemistry) dissociates] as a leaving group and the other half of the substrate dissociates from the enzyme.
-# The negative oxygen on serine readily accepts the hydrogen from histadine and in doing so regenerates the active site of the enzyme.
+# The negative oxygen on serine readily accepts the hydrogen from histidine and in doing so regenerates the active site of the enzyme.
   </div>