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3nty

From Proteopedia

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Current revision

Crystal structure of AKR1C1 in complex with NADP and 5-Phenyl,3-chlorosalicylic acid

Structural highlights

3nty is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.87Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AK1C1_HUMAN Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.^[1] ^[2]

Publication Abstract from PubMed

Human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) is an important drug target due to its role in the development of lung and endometrial cancers, premature birth and neuronal disorders. We report the crystal structure of AKR1C1 complexed with the first structure-based designed inhibitor 3-chloro-5-phenylsalicylic acid (K(i)=0.86nM) bound in the active site. The binding of 3-chloro-5-phenylsalicylic acid to AKR1C1 resulted in a conformational change in the side chain of Phe311 to accommodate the bulky phenyl ring substituent at the 5-position of the inhibitor. The contributions of the nonconserved residues Leu54, Leu306, Leu308 and Phe311 to the binding were further investigated by site-directed mutagenesis, and the effects of the mutations on the K(i) value were determined. The Leu54Val and Leu306Ala mutations resulted in 6- and 81-fold increases, respectively, in K(i) values compared to the wild-type enzyme, while the remaining mutations had little or no effects.

Probing the inhibitor selectivity pocket of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis.,El-Kabbani O, Dhagat U, Soda M, Endo S, Matsunaga T, Hara A Bioorg Med Chem Lett. 2011 Apr 15;21(8):2564-7. Epub 2011 Jan 22. PMID:21414777^[3]

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

References

↑ Zhang Y, Dufort I, Rheault P, Luu-The V. Characterization of a human 20alpha-hydroxysteroid dehydrogenase. J Mol Endocrinol. 2000 Oct;25(2):221-8. PMID:11013348
↑ Hara A, Matsuura K, Tamada Y, Sato K, Miyabe Y, Deyashiki Y, Ishida N. Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells. Biochem J. 1996 Jan 15;313 ( Pt 2):373-6. PMID:8573067
↑ El-Kabbani O, Dhagat U, Soda M, Endo S, Matsunaga T, Hara A. Probing the inhibitor selectivity pocket of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2564-7. Epub 2011 Jan 22. PMID:21414777 doi:10.1016/j.bmcl.2011.01.076

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3nty"

Categories: Homo sapiens | Large Structures | Dhagat U | El-Kabbani O

@@ Line 3: / Line 3: @@
 <StructureSection load='3nty' size='340' side='right'caption='[[3nty]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3nty]] 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=3NTY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3NTY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3nty]] 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=3NTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NTY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5P3:5-CHLORO-4-HYDROXYBIPHENYL-3-CARBOXYLIC+ACID'>5P3</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.87&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3nty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nty OCA], [http://pdbe.org/3nty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nty RCSB], [http://www.ebi.ac.uk/pdbsum/3nty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nty ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5P3:5-CHLORO-4-HYDROXYBIPHENYL-3-CARBOXYLIC+ACID'>5P3</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3nty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nty OCA], [https://pdbe.org/3nty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nty RCSB], [https://www.ebi.ac.uk/pdbsum/3nty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nty ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/AK1C1_HUMAN AK1C1_HUMAN]] Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.<ref>PMID:11013348</ref> <ref>PMID:8573067</ref>
+[https://www.uniprot.org/uniprot/AK1C1_HUMAN AK1C1_HUMAN] Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.<ref>PMID:11013348</ref> <ref>PMID:8573067</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Dhagat, U]]
+[[Category: Dhagat U]]
-[[Category: El-Kabbani, O]]
+[[Category: El-Kabbani O]]
-[[Category: 20 alpha hydroxysteroid dehydrogenase]]
-[[Category: Akr1c1]]
-[[Category: Aldo-keto reductase]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

3nty

From Proteopedia

Current revision

Crystal structure of AKR1C1 in complex with NADP and 5-Phenyl,3-chlorosalicylic acid

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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