1fdv

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[[Image:1fdv.jpg|left|200px]]
[[Image:1fdv.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1fdv |SIZE=350|CAPTION= <scene name='initialview01'>1fdv</scene>, resolution 3.1&Aring;
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The line below this paragraph, containing "STRUCTURE_1fdv", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=CAT:Catalytic+Site'>CAT</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1fdv| PDB=1fdv | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fdv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fdv OCA], [http://www.ebi.ac.uk/pdbsum/1fdv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fdv RCSB]</span>
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}}
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'''HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221L COMPLEXED WITH NAD+'''
'''HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221L COMPLEXED WITH NAD+'''
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[[Category: Mazza, C.]]
[[Category: Mazza, C.]]
[[Category: 17-beta-hydroxysteroid]]
[[Category: 17-beta-hydroxysteroid]]
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[[Category: dehydrogenase]]
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[[Category: Dehydrogenase]]
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[[Category: mutant]]
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[[Category: Mutant]]
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[[Category: nad]]
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[[Category: Nad]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:13:01 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:21:09 2008''
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Revision as of 13:13, 2 May 2008

Image:1fdv.jpg

Template:STRUCTURE 1fdv

HUMAN 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 MUTANT H221L COMPLEXED WITH NAD+


Overview

Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the short chain dehydrogenase reductase (SDR) family, is responsible for the synthesis of 17beta-estradiol, the biologically active estrogen involved in the genesis and development of human breast cancers. Here, we report the crystal structures of the H221L 17beta-HSD1 mutant complexed to NADP+ and estradiol and the H221L mutant/NAD+ and a H221Q mutant/estradiol complexes. These structures provide a complete picture of the NADP+-enzyme interactions involving the flexible 191-199 loop (well ordered in the H221L mutant) and suggest that the hydrophobic residues Phe192-Met193 could facilitate hydride transfer. 17beta-HSD1 appears to be unique among the members of the SDR protein family in that one of the two basic residues involved in the charge compensation of the 2'-phosphate does not belong to the Rossmann-fold motif. The remarkable stabilization of the NADP+ 2'-phosphate by the enzyme also clearly establishes its preference for this cofactor relative to NAD+. Analysis of the catalytic properties of, and estradiol binding to, the two mutants suggests that the His221-steroid O3 hydrogen bond plays an important role in substrate specificity.

About this Structure

1FDV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase., Mazza C, Breton R, Housset D, Fontecilla-Camps JC, J Biol Chem. 1998 Apr 3;273(14):8145-52. PMID:9525918 Page seeded by OCA on Fri May 2 16:13:01 2008

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