1wpl: Difference between revisions

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[[Image:1wpl.gif|left|200px]]<br /><applet load="1wpl" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1wpl.gif|left|200px]]<br /><applet load="1wpl" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1wpl, resolution 2.8Å" />

'''Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex'''<br />

==Overview==

GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the, biosynthesis of tetrahydrobiopterin, a key cofactor necessary for nitric, oxide synthase and for the hydroxylases that are involved in the, production of catecholamines and serotonin. In animals, the GTPCHI, feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward, activation of GTPCHI activity in the presence of phenylalanine, whereas it, induces feedback inhibition of enzyme activity in the presence of, biopterin. Here, we have reported the crystal structure of the, biopterin-induced inhibitory complex of GTPCHI and GFRP and compared it, with the previously reported phenylalanine-induced stimulatory complex., The structure reveals five biopterin molecules located at each interface, between GTPCHI and GFRP. Induced fitting structural changes by the, biopterin binding expand large conformational changes in GTPCHI peptide, segments forming the active site, resulting in inhibition of the activity., By locating 3,4-dihydroxy-phenylalanine-responsive dystonia mutations in, the complex structure, we found mutations that may possibly disturb the, GFRP-mediated regulation of GTPCHI.

GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the biosynthesis of tetrahydrobiopterin, a key cofactor necessary for nitric oxide synthase and for the hydroxylases that are involved in the production of catecholamines and serotonin. In animals, the GTPCHI feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward activation of GTPCHI activity in the presence of phenylalanine, whereas it induces feedback inhibition of enzyme activity in the presence of biopterin. Here, we have reported the crystal structure of the biopterin-induced inhibitory complex of GTPCHI and GFRP and compared it with the previously reported phenylalanine-induced stimulatory complex. The structure reveals five biopterin molecules located at each interface between GTPCHI and GFRP. Induced fitting structural changes by the biopterin binding expand large conformational changes in GTPCHI peptide segments forming the active site, resulting in inhibition of the activity. By locating 3,4-dihydroxy-phenylalanine-responsive dystonia mutations in the complex structure, we found mutations that may possibly disturb the GFRP-mediated regulation of GTPCHI.

==About this Structure==

1WPL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with NA, ZN, HBI and 3PO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1WPL OCA].

1WPL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HBI:'>HBI</scene> and <scene name='pdbligand=3PO:'>3PO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WPL OCA].

==Reference==

Line 24:

[[Category: enzyme-regulatory protein complex]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:50 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1wpl.gif|left|200px]]<br /><applet load="1wpl" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1wpl.gif|left|200px]]<br /><applet load="1wpl" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1wpl, resolution 2.8&Aring;" />
 '''Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex'''<br />
 ==Overview==
-GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the, biosynthesis of tetrahydrobiopterin, a key cofactor necessary for nitric, oxide synthase and for the hydroxylases that are involved in the, production of catecholamines and serotonin. In animals, the GTPCHI, feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward, activation of GTPCHI activity in the presence of phenylalanine, whereas it, induces feedback inhibition of enzyme activity in the presence of, biopterin. Here, we have reported the crystal structure of the, biopterin-induced inhibitory complex of GTPCHI and GFRP and compared it, with the previously reported phenylalanine-induced stimulatory complex., The structure reveals five biopterin molecules located at each interface, between GTPCHI and GFRP. Induced fitting structural changes by the, biopterin binding expand large conformational changes in GTPCHI peptide, segments forming the active site, resulting in inhibition of the activity., By locating 3,4-dihydroxy-phenylalanine-responsive dystonia mutations in, the complex structure, we found mutations that may possibly disturb the, GFRP-mediated regulation of GTPCHI.
+GTP cyclohydrolase I (GTPCHI) is the rate-limiting enzyme involved in the biosynthesis of tetrahydrobiopterin, a key cofactor necessary for nitric oxide synthase and for the hydroxylases that are involved in the production of catecholamines and serotonin. In animals, the GTPCHI feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward activation of GTPCHI activity in the presence of phenylalanine, whereas it induces feedback inhibition of enzyme activity in the presence of biopterin. Here, we have reported the crystal structure of the biopterin-induced inhibitory complex of GTPCHI and GFRP and compared it with the previously reported phenylalanine-induced stimulatory complex. The structure reveals five biopterin molecules located at each interface between GTPCHI and GFRP. Induced fitting structural changes by the biopterin binding expand large conformational changes in GTPCHI peptide segments forming the active site, resulting in inhibition of the activity. By locating 3,4-dihydroxy-phenylalanine-responsive dystonia mutations in the complex structure, we found mutations that may possibly disturb the GFRP-mediated regulation of GTPCHI.
 ==About this Structure==
-WPL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with NA, ZN, HBI and 3PO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1WPL OCA].
+WPL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HBI:'>HBI</scene> and <scene name='pdbligand=3PO:'>3PO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/GTP_cyclohydrolase_I GTP cyclohydrolase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.16 3.5.4.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WPL OCA].
 ==Reference==
@@ Line 24: / Line 24: @@
 [[Category: enzyme-regulatory protein complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 05:35:03 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:50 2008''