8gk3: Difference between revisions

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<table><tr><td colspan='2'>[[8gk3]] is a 12 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=8GK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GK3 FirstGlance]. <br>
<table><tr><td colspan='2'>[[8gk3]] is a 12 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=8GK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GK3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZQK:Dehydroepiandrosterone+sulfate'>ZQK</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZWY:[(3~{S},8~{R},9~{S},10~{R},13~{S},14~{S})-10,13-dimethyl-17-oxidanylidene-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl]+hydrogen+sulfate'>ZWY</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gk3 OCA], [https://pdbe.org/8gk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gk3 RCSB], [https://www.ebi.ac.uk/pdbsum/8gk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gk3 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gk3 OCA], [https://pdbe.org/8gk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gk3 RCSB], [https://www.ebi.ac.uk/pdbsum/8gk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gk3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/CP3A7_HUMAN CP3A7_HUMAN] A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:9555064, PubMed:11093772, PubMed:14559847, PubMed:12865317, PubMed:17178770). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:9555064, PubMed:11093772, PubMed:14559847, PubMed:12865317, PubMed:17178770). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:9555064, PubMed:17178770). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:14559847, PubMed:12865317). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064).<ref>PMID:11093772</ref> <ref>PMID:12865317</ref> <ref>PMID:14559847</ref> <ref>PMID:17178770</ref> <ref>PMID:9555064</ref>
[https://www.uniprot.org/uniprot/CP3A7_HUMAN CP3A7_HUMAN] A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064).<ref>PMID:11093772</ref> <ref>PMID:12865317</ref> <ref>PMID:14559847</ref> <ref>PMID:17178770</ref> <ref>PMID:9555064</ref>  
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== Publication Abstract from PubMed ==
Human fetal cytochrome P450 3A7 (CYP3A7) is involved in both xenobiotic metabolism and the estriol biosynthetic pathway. Although much is understood about cytochrome P450 3A4 (CYP3A4) and its role in adult drug metabolism, CYP3A7 is poorly characterized in terms of its interactions with both categories of substrates. Herein, a crystallizable mutated form of CYP3A7 was saturated with its primary endogenous substrate dehydroepiandrosterone 3-sulfate (DHEA-S) to yield a 2.6 A X-ray structure revealing the unexpected capacity to simultaneously bind four copies of DHEA-S. Two DHEA-S molecules are located in the active site proper, one in a ligand access channel, and one on the hydrophobic F'-G' surface normally embedded in the membrane. While neither DHEA-S binding or metabolism exhibit cooperative kinetics, the current structure is consistent with cooperativity common to CYP3A enzymes. Overall, this information suggests that mechanism(s) of CYP3A7 interactions with steroidal substrates are complex.
 
Human Cytochrome P450 3A7 Binding Four Copies of Its Native Substrate Dehydroepiandrosterone 3-Sulfate.,Liu J, Kandel SE, Lampe JN, Scott EE J Biol Chem. 2023 Jun 29:104993. doi: 10.1016/j.jbc.2023.104993. PMID:37392852<ref>PMID:37392852</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8gk3" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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<references/>

Latest revision as of 15:18, 13 August 2026

Cytochrome P450 3A7 in complex with Dehydroepiandrosterone sulfate

8gk3, resolution 2.60Å

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