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==Crystal Structure of CYP1B1 and Inhibitor Having Azide Group== | ==Crystal Structure of CYP1B1 and Inhibitor Having Azide Group== | ||
<StructureSection load='6iq5' size='340' side='right' caption='[[6iq5]], [[Resolution|resolution]] 3.70Å' scene=''> | <StructureSection load='6iq5' size='340' side='right'caption='[[6iq5]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6iq5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IQ5 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6iq5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IQ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IQ5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AQ0:2-(cis-4-azidocyclohexyl)-4H-naphtho[1,2-b]pyran-4-one'>AQ0</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AQ0:2-(cis-4-azidocyclohexyl)-4H-naphtho[1,2-b]pyran-4-one'>AQ0</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6iq5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iq5 OCA], [https://pdbe.org/6iq5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iq5 RCSB], [https://www.ebi.ac.uk/pdbsum/6iq5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iq5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/CP1B1_HUMAN CP1B1_HUMAN] Peters anomaly;Congenital glaucoma;Primary adult open-angle glaucoma;Juvenile glaucoma. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. CYP1B1 mutations have been reported to pose a significant risk for early-onset POAG and also modify glaucoma phenotype in patients who do not carry a MYOC mutation (PubMed:15342693).<ref>PMID:15342693</ref> The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult-onset and juvenile forms of open angle glaucoma (PubMed:11774072). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (PubMed:11774072).<ref>PMID:11774072</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/CP1B1_HUMAN CP1B1_HUMAN] Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.<ref>PMID:10426814</ref> <ref>PMID:15258110</ref> <ref>PMID:22888116</ref> <ref>PMID:23821647</ref> | ||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Itoh T]] | ||
[[Category: | [[Category: Kubo M]] | ||
[[Category: | [[Category: Yamamoto K]] | ||
Latest revision as of 13:34, 27 March 2024
Crystal Structure of CYP1B1 and Inhibitor Having Azide GroupCrystal Structure of CYP1B1 and Inhibitor Having Azide Group
Structural highlights
DiseaseCP1B1_HUMAN Peters anomaly;Congenital glaucoma;Primary adult open-angle glaucoma;Juvenile glaucoma. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. CYP1B1 mutations have been reported to pose a significant risk for early-onset POAG and also modify glaucoma phenotype in patients who do not carry a MYOC mutation (PubMed:15342693).[1] The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult-onset and juvenile forms of open angle glaucoma (PubMed:11774072). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (PubMed:11774072).[2] FunctionCP1B1_HUMAN Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.[3] [4] [5] [6] See AlsoReferences
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