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1fdt

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Revision as of 07:03, 24 March 2021

HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 COMPLEXED WITH ESTRADIOL AND NADP+

Structural highlights

1fdt is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	17-beta-estradiol 17-dehydrogenase, with EC number 1.1.1.62
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DHB1_HUMAN] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND: The steroid hormone 17beta-estradiol is important in the genesis and development of human breast cancer. Its intracellular concentration is regulated by 17beta-hydroxysteroid dehydrogenase, which catalyzes the reversible reduction of estrone to 17beta-estradiol. This enzyme is thus an important target for inhibitor design. The precise localization and orientation of the substrate and cofactor in the active site is of paramount importance for the design of such inhibitors, and for an understanding of the catalytic mechanism. RESULTS: The structure of recombinant human 17beta-hydroxysteroid dehydrogenase of type 1 (17beta-HSD1) in complex with estradiol at room temperature has been determined at 1.7 A resolution, and a ternary 17betaHSD1-estradiol-NADP+ complex at -150 degrees C has been solved and refined at 2.20 A resolution. The structures show that estradiol interacts with the enzyme through three hydrogen bonds (involving side chains of Ser142, Tyr155 and His221), and hydrophobic interactions between the core of the steroid and nine other residues. The NADP+ molecule binds in an extended conformation, with the nicotinamide ring close to the estradiol molecule. CONCLUSIONS: From the structure of the complex of the enzyme with the substrate and cofactor of the oxidation reaction, the orientation of the substrates for the reduction reaction can be deduced with confidence. A triangular hydrogen-bond network between Tyr155, Ser142 and O17 from estradiol probably facilitates the deprotonation of the reactive tyrosine, while the conserved Lys159 appears not to be directly involved in catalysis. Both the steroid-binding site and the NADPH-binding site can be proposed as targets for the design of inhibitors.

The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors.,Breton R, Housset D, Mazza C, Fontecilla-Camps JC Structure. 1996 Aug 15;4(8):905-15. PMID:8805577^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Breton R, Housset D, Mazza C, Fontecilla-Camps JC. The structure of a complex of human 17beta-hydroxysteroid dehydrogenase with estradiol and NADP+ identifies two principal targets for the design of inhibitors. Structure. 1996 Aug 15;4(8):905-15. PMID:8805577

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fdt"

@@ Line 3: / Line 3: @@
 <StructureSection load='1fdt' size='340' side='right'caption='[[1fdt]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fdt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FDT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FDT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fdt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FDT FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EST:ESTRADIOL'>EST</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EST:ESTRADIOL'>EST</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </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=1fdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fdt OCA], [http://pdbe.org/1fdt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fdt RCSB], [http://www.ebi.ac.uk/pdbsum/1fdt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fdt 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=1fdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fdt OCA], [https://pdbe.org/1fdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fdt RCSB], [https://www.ebi.ac.uk/pdbsum/1fdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fdt ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN]] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
+[[https://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN]] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
+*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
 == References ==
 <references/>

1fdt

From Proteopedia

Revision as of 07:03, 24 March 2021

HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 COMPLEXED WITH ESTRADIOL AND NADP+

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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