2hsd
From Proteopedia
(New page: 200px<br /><applet load="2hsd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hsd, resolution 2.64Å" /> '''THE REFINED THREE-DI...) |
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| - | [[Image:2hsd.gif|left|200px]]<br /><applet load="2hsd" size=" | + | [[Image:2hsd.gif|left|200px]]<br /><applet load="2hsd" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2hsd, resolution 2.64Å" /> | caption="2hsd, resolution 2.64Å" /> | ||
'''THE REFINED THREE-DIMENSIONAL STRUCTURE OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE AND POSSIBLE ROLES OF THE RESIDUES CONSERVED IN SHORT-CHAIN DEHYDROGENASES'''<br /> | '''THE REFINED THREE-DIMENSIONAL STRUCTURE OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE AND POSSIBLE ROLES OF THE RESIDUES CONSERVED IN SHORT-CHAIN DEHYDROGENASES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Bacterial 3 alpha,20 beta-hydroxysteroid dehydrogenase | + | BACKGROUND: Bacterial 3 alpha,20 beta-hydroxysteroid dehydrogenase reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of steroids derived from androstanes and pregnanes. It was the first short-chain dehydrogenase to be studied by X-ray crystallography. The previous description of the structure of this enzyme, at 2.6 A resolution, did not permit unambiguous assignment of several important groups. We have further refined the structure of the complex of the enzyme with its cofactor, nicotinamide adenine dinucleotide (NAD), and solvent molecules, at the same resolution. RESULTS: The asymmetric unit of the crystal contains four monomers, each with 253 amino acid residues, 38 water molecules, and 176 cofactor atoms belonging to four NAD molecules--one for each subunit. The positioning of the cofactor molecule has been modified from our previous model and is deeper in the catalytic cavity as observed for other members of both the long-chain and short-chain dehydrogenase families. The nicotinamide-ribose end of the cofactor has several possible conformations or is dynamically disordered. CONCLUSIONS: The catalytic site contains residues Tyr152 and Lys156. These two amino acids are strictly conserved in the short-chain dehydrogenase superfamily. Modeling studies with a cortisone molecule in the catalytic site suggest that the Tyr152, Lys156 and Ser139 side chains promote electrophilic attack on the (C20-O) carbonyl oxygen atom, thus enabling the carbon atom to accept a hydride from the reduced cofactor. |
==About this Structure== | ==About this Structure== | ||
| - | 2HSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_exfoliatus Streptomyces exfoliatus] with NAD as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 2HSD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_exfoliatus Streptomyces exfoliatus] with <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 1HSD. Active as [http://en.wikipedia.org/wiki/3-alpha-(or_20-beta)-hydroxysteroid_dehydrogenase 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.53 1.1.1.53] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HSD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Streptomyces exfoliatus]] | [[Category: Streptomyces exfoliatus]] | ||
| - | [[Category: Duax, W | + | [[Category: Duax, W L.]] |
[[Category: Ghosh, D.]] | [[Category: Ghosh, D.]] | ||
[[Category: NAD]] | [[Category: NAD]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:45:11 2008'' |
Revision as of 15:45, 21 February 2008
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THE REFINED THREE-DIMENSIONAL STRUCTURE OF 3ALPHA,20BETA-HYDROXYSTEROID DEHYDROGENASE AND POSSIBLE ROLES OF THE RESIDUES CONSERVED IN SHORT-CHAIN DEHYDROGENASES
Overview
BACKGROUND: Bacterial 3 alpha,20 beta-hydroxysteroid dehydrogenase reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of steroids derived from androstanes and pregnanes. It was the first short-chain dehydrogenase to be studied by X-ray crystallography. The previous description of the structure of this enzyme, at 2.6 A resolution, did not permit unambiguous assignment of several important groups. We have further refined the structure of the complex of the enzyme with its cofactor, nicotinamide adenine dinucleotide (NAD), and solvent molecules, at the same resolution. RESULTS: The asymmetric unit of the crystal contains four monomers, each with 253 amino acid residues, 38 water molecules, and 176 cofactor atoms belonging to four NAD molecules--one for each subunit. The positioning of the cofactor molecule has been modified from our previous model and is deeper in the catalytic cavity as observed for other members of both the long-chain and short-chain dehydrogenase families. The nicotinamide-ribose end of the cofactor has several possible conformations or is dynamically disordered. CONCLUSIONS: The catalytic site contains residues Tyr152 and Lys156. These two amino acids are strictly conserved in the short-chain dehydrogenase superfamily. Modeling studies with a cortisone molecule in the catalytic site suggest that the Tyr152, Lys156 and Ser139 side chains promote electrophilic attack on the (C20-O) carbonyl oxygen atom, thus enabling the carbon atom to accept a hydride from the reduced cofactor.
About this Structure
2HSD is a Single protein structure of sequence from Streptomyces exfoliatus with as ligand. This structure supersedes the now removed PDB entry 1HSD. Active as 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase, with EC number 1.1.1.53 Full crystallographic information is available from OCA.
Reference
The refined three-dimensional structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases., Ghosh D, Wawrzak Z, Weeks CM, Duax WL, Erman M, Structure. 1994 Jul 15;2(7):629-40. PMID:7922040
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