We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

3s79

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:48, 14 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
==Human placental aromatase cytochrome P450 (CYP19A1) refined at 2.75 angstrom==
==Human placental aromatase cytochrome P450 (CYP19A1) refined at 2.75 angstrom==
-
<StructureSection load='3s79' size='340' side='right' caption='[[3s79]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
+
<StructureSection load='3s79' size='340' side='right'caption='[[3s79]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[3s79]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S79 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S79 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[3s79]] is a 1 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=3S79 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S79 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASD:4-ANDROSTENE-3-17-DIONE'>ASD</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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]] 2.75&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3s7s|3s7s]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASD:4-ANDROSTENE-3-17-DIONE'>ASD</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP19A1, ARO1, CYAR, CYP19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3s79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s79 OCA], [https://pdbe.org/3s79 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s79 RCSB], [https://www.ebi.ac.uk/pdbsum/3s79 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s79 ProSAT]</span></td></tr>
-
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>
+
-
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s79 OCA], [http://pdbe.org/3s79 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s79 RCSB], [http://www.ebi.ac.uk/pdbsum/3s79 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s79 ProSAT]</span></td></tr>
+
</table>
</table>
== Disease ==
== Disease ==
-
[[http://www.uniprot.org/uniprot/CP19A_HUMAN CP19A_HUMAN]] Defects in CYP19A1 are a cause of aromatase excess syndrome (AEXS) [MIM:[http://omim.org/entry/139300 139300]]; also known as familial gynecomastia. AEXS is characterized by an estrogen excess due to an increased aromatase activity. Defects in CYP19A1 are the cause of aromatase deficiency (AROD) [MIM:[http://omim.org/entry/613546 613546]]. AROD is a rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.<ref>PMID:8265607</ref> <ref>PMID:8530621</ref> <ref>PMID:9211678</ref>
+
[https://www.uniprot.org/uniprot/CP19A_HUMAN CP19A_HUMAN] Defects in CYP19A1 are a cause of aromatase excess syndrome (AEXS) [MIM:[https://omim.org/entry/139300 139300]; also known as familial gynecomastia. AEXS is characterized by an estrogen excess due to an increased aromatase activity. Defects in CYP19A1 are the cause of aromatase deficiency (AROD) [MIM:[https://omim.org/entry/613546 613546]. AROD is a rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.<ref>PMID:8265607</ref> <ref>PMID:8530621</ref> <ref>PMID:9211678</ref>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/CP19A_HUMAN CP19A_HUMAN]] Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
+
[https://www.uniprot.org/uniprot/CP19A_HUMAN CP19A_HUMAN] Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
Human cytochrome P450 aromatase catalyzes with high specificity the synthesis of estrogens from androgens. Aromatase inhibitors (AIs) such as exemestane, 6-methylidene-androsta-1,4-diene-3,17-dione, are preeminent drugs for the treatment of estrogen-dependent breast cancer. The crystal structure of human placental aromatase has shown an androgen-specific active site. By utilizing the structural data, novel C6-substituted androsta-1,4-diene-3,17-dione inhibitors have been designed. Several of the C6-substituted 2-alkynyloxy compounds inhibit purified placental aromatase with IC50s in the nM range. Anti-proliferation studies in a MCF-7 breast cancer cell line demonstrate that some of these compounds have EC50s better than 1nM, exceeding exemestane. X-ray structures of aromatase-complexes of two potent compounds reveal that, per their design, the novel side groups protrude into the opening to the access channel unoccupied in the enzyme-substrate/exemestane complexes. The observed structure-activity relationship is borne out by the X-ray data. Structure-guided design permits utilization of the aromatase-specific interactions for the development of next generation AIs.
+
-
Novel Aromatase Inhibitors By Structure-Guided Design.,Ghosh D, Lo J, Xi J, Hubbell S, Egbuta C, Jiang W, An J, Morton D, Valette D, Griswold J, Davies HM J Med Chem. 2012 Sep 5. PMID:22951074<ref>PMID:22951074</ref>
+
==See Also==
-
 
+
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 3s79" style="background-color:#fffaf0;"></div>
+
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
-
[[Category: Unspecific monooxygenase]]
+
[[Category: Large Structures]]
-
[[Category: Ghosh, D]]
+
[[Category: Ghosh D]]
-
[[Category: Oxidoreductase]]
+

Current revision

Human placental aromatase cytochrome P450 (CYP19A1) refined at 2.75 angstrom

PDB ID 3s79

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3s79"
Personal tools