This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3fjn

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 21:30, 25 December 2014

The crystal structure of 17-alpha hydroxysteroid dehydrogenase Y224D mutant.

Structural highlights

3fjn is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	3(or 17)-alpha-hydroxysteroid dehydrogenase, with EC number 1.1.1.209
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[AK1CL_MOUSE] NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids.^[1] ^[2] ^[3]

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

Mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21) is the only aldo-keto reductase that catalyzes the stereospecific reduction of 3- and 17-ketosteroids to the corresponding 3(17)alpha-hydroxysteroids. The Y224D mutation of AKR1C21 reduced the K(m) value for NADP(H) by up to 80-fold and completely reversed the 17alpha stereospecificity of the enzyme. The crystal structure of the Y224D mutant at 2.3 A resolution revealed that the mutation resulted in a change in the conformation of the flexible loop B, including the V-shaped groove, which is a unique feature of the active-site architecture of wild-type AKR1C21 and is formed by the side chains of Tyr224 and Trp227. Furthermore, mutations (Y224F and Q222N) of residues involved in forming the safety belt for binding of the coenzyme showed similar alterations in kinetic constants for 3alpha-hydroxy/3-ketosteroids and 17-hydroxy/ketosteroids compared with the wild type.

Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme.,Dhagat U, Endo S, Mamiya H, Hara A, El-Kabbani O Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):198-204. Epub 2010, Jan 22. PMID:20124700^[4]

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

References

↑ Ishikura S, Usami N, Nakajima S, Kameyama A, Shiraishi H, Carbone V, El-Kabbani O, Hara A. Characterization of two isoforms of mouse 3(17)alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase family. Biol Pharm Bull. 2004 Dec;27(12):1939-45. PMID:15577209
↑ Bellemare V, Faucher F, Breton R, Luu-The V. Characterization of 17alpha-hydroxysteroid dehydrogenase activity (17alpha-HSD) and its involvement in the biosynthesis of epitestosterone. BMC Biochem. 2005 Jul 14;6:12. PMID:16018803 doi:http://dx.doi.org/1471-2091-6-12
↑ Faucher F, Pereira de Jesus-Tran K, Cantin L, Luu-The V, Labrie F, Breton R. Crystal structures of mouse 17alpha-hydroxysteroid dehydrogenase (apoenzyme and enzyme-NADP(H) binary complex): identification of molecular determinants responsible for the unique 17alpha-reductive activity of this enzyme. J Mol Biol. 2006 Dec 8;364(4):747-63. Epub 2006 Sep 16. PMID:17034817 doi:http://dx.doi.org/10.1016/j.jmb.2006.09.030
↑ Dhagat U, Endo S, Mamiya H, Hara A, El-Kabbani O. Studies on a Tyr residue critical for the binding of coenzyme and substrate in mouse 3(17)alpha-hydroxysteroid dehydrogenase (AKR1C21): structure of the Y224D mutant enzyme. Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):198-204. Epub 2010, Jan 22. PMID:20124700 doi:10.1107/S0907444909051464

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/3fjn"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3fjn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FJN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FJN FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3(or_17)-alpha-hydroxysteroid_dehydrogenase 3(or 17)-alpha-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.209 1.1.1.209] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3(or_17)-alpha-hydroxysteroid_dehydrogenase 3(or 17)-alpha-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.209 1.1.1.209] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3fjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fjn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fjn RCSB], [http://www.ebi.ac.uk/pdbsum/3fjn PDBsum]</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=3fjn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fjn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fjn RCSB], [http://www.ebi.ac.uk/pdbsum/3fjn PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/AK1CL_MOUSE AK1CL_MOUSE]] NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids.<ref>PMID:15577209</ref> <ref>PMID:16018803</ref> <ref>PMID:17034817</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Mus musculus]]
-[[Category: Dhagat, U.]]
+[[Category: Dhagat, U]]
-[[Category: El-Kabbani, O.]]
+[[Category: El-Kabbani, O]]
 [[Category: 17-alpha-hydroxysteroid dehydrogenase]]
 [[Category: Aldo-keto reductase]]

3fjn

From Proteopedia

Revision as of 21:30, 25 December 2014

The crystal structure of 17-alpha hydroxysteroid dehydrogenase Y224D mutant.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox