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| <!-- | | <StructureSection load='1lwi' size='350' side='right' scene='49/491805/Cv/1' caption='Rat 3-α hydroxysteroid dehydrogenase dimer complex with cofactor NADP [[1lwi]]'> |
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| '''Hydroxysteroid dehydrogenase''' (HSD) catalyzes the dehydrogenation of hydroxysteroids. HSD is classdified according to the number of carbon it is acting on. 3-α HSD catalyzes the conversion of androsterone to 5α-androstane-3, 17-dione and 17-α estradiol to estrone. 3-α HSD (also named 17-α HSD) is a bile acid-metabolizing enzyme. 7-α HSD is involved in the dehydrogenation of cholanate compounds and is a bile acid-inducible enzyme. 20-α HSD is involved in the control of progesterone level in pregnancy of mice. 11-β HSD converts 11-keto products like cortisone to cortisol. 17-β HSD is involved in the conversion of androstenedione to testosterone. 3-β/17-β HSD catalyzes the reversible dehydrogenation of steroid compounds at position 3 and 17. NAD and NADP are cofactors of HSD. | |
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| ==3D structures of hydroxysteroid dehydrogenase== | | == Function == |
| | '''Hydroxysteroid dehydrogenase''' (HSD) catalyzes the dehydrogenation of hydroxysteroids. HSD is classified according to the number of the carbon it is acting on.<br /> |
| | * '''3-α HSD''' catalyzes the conversion of androsterone to 5α-androstane-3, 17-dione and 17-α estradiol to estrone. 3-α HSD (also named 17-α HSD) is a bile acid-metabolizing enzyme<ref>PMID:12810547</ref>.<br /> |
| | * '''7-α HSD''' is involved in the dehydrogenation of cholanate compounds and is a bile acid-inducible enzyme<ref>PMID:786279</ref>.<br /> |
| | * '''20-α HSD''' is involved in the control of progesterone level in pregnancy of mice<ref>PMID:17122075</ref>.<br /> |
| | * '''11-β HSD''' converts 11-keto products like cortisone to cortisol<ref>PMID:15466942</ref>.<br /> |
| | * '''17-β HSD''' is involved in the conversion of androstenedione to testosterone<ref>PMID:9029730</ref>. See [[Human Keto Acyl Reductase]].<br /> |
| | * '''3-β/17-β HSD''' catalyzes the reversible dehydrogenation of steroid compounds at position 3 and 17<ref>PMID:1309351</ref>.<br /> |
| | [[NAD]] and NADP are cofactors of HSD. |
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| '''3-α HSD '''
| | == Disease == |
| | Deficiency of 17-β HSD caused by mutations are the cause of male hermaphroditism<ref>PMID:10599740</ref>. Deficiency of 3-β HSD caused by mutations are the cause of congenital adrenal hyperplasia<ref>PMID:10599696</ref>. Deficiency of 11-β HSD is associated with alcoholic and non-alcoholic chronic liver disease<ref>PMID:8445034</ref>. |
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| [[1ral]] – rHSD – rat<BR />
| | == Structural highlights == |
| [[1fjh]] - CtHSD – ''Comamonas testosterone''<BR />
| | The structure of 3-α HSD is that of an <scene name='49/491805/Cv/5'>α/β barrel</scene> with the <scene name='49/491805/Cv/6'>cofactor NADP binding site</scene> at the C-terminal of the barrel<ref>PMID:8718859</ref>. Water molecules shown as red spheres. |
| [[3fjn]] - mHSD (mutant) - mouse
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| ''3-α HSD binary complex''
| | ==3D structures of hydroxysteroid dehydrogenase== |
| | | [[Hydroxysteroid dehydrogenase 3D structures]] |
| [[1lwi]] – rHSD + NADP<BR />
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| [[1fk8]] – CtHSD + NAD<BR />
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| [[2fvl]], [[2hdj]], [[2fgb]] - hHSD + NADP<BR />
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| [[2dkn]] - HSD + NAD – ''Pseudomonas''<BR />
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| [[2p5n]] - mHSD + NADP<BR />
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| ''3-α HSD ternary complex''
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| [[1ihi]], [[1j96]] - hHSD + hydroxysteroid + NADP – human<BR />
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| [[1ry0]] - hHSD + prostaglandin + NADP<BR />
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| [[1ry8]] - hHSD + rutin + NADP<BR />
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| [[2f38]] - hHSD + bimatoprost + NADP<BR />
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| [[1afs]] - rHSD + hydroxysteroid + NADP<BR />
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| [[2ipf]] - mHSD + hydroxysteroid + NADP<BR />
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| [[2ipg]], [[2ipj]] - mHSD (mutant) + hydroxysteroid + NADP<BR />
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| [[3cv6]] - mHSD (mutant) + inhibitor + NADP<BR />
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| '''7-α HSD'''
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| [[3gaf]] - HSD – ''Brucella melitensis''<BR />
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| [[1ahh]] – EcHSD + NAD – ''Escherichia coli''<BR />
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| [[1ahi]], [[1fmc]] – EcHSD + hydroxysteroid + NAD
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| '''20-α HSD'''
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| [[1q5m]] - raHSD + NADP – rabbit
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| ''20-α HSD ternary complex''
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| [[1mrq]] – hHSD + hydroxysteroid + NADP<BR />
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| [[3c3u]], [[3nty]] - hHSD + inhibitor + NADP<BR />
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| [[3gug]] - hHSD (mutant) + inhibitor + NADP<BR />
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| [[1q13]] - raHSD + hydroxysteroid + NADP<BR />
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| '''11-β HSD'''
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| [[1xu7]], [[1xu9]] - hHSD (mutant) + NADP<BR />
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| [[2pd6]] - hHSD + NAD<BR />
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| [[1y5m]] - mHSD + NADP<BR />
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| [[1xse]] - gpHSD catalytic domain + NADP – guinea pig<BR />
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| [[3hb4]] - hHSD + inhibitor<BR />
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| [[3dey]] - hHSD + hydroxysteroid<BR />
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| [[3dwf]], [[3lz6]] - gpHSD catalytic domain (mutant) + NADP<BR />
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| ''11-β HSD ternary complex''
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| [[3g49]] - gpHSD catalytic domain + inhibitor + NADP<BR />
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| [[1y5r]], [[3gmd]] - mHSD + hydroxysteroid + NADP<BR />
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| [[2bel]] - hHSD + hydroxysteroid + NADP<BR />
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| [[2irw]], [[2ilt]] - hHSD + inhibitor + NADP<BR />
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| [[2rbe]], [[3byz]], [[3bzu]], [[3ch6]], [[3czr]], [[3d3e]], [[3d4n]], [[3d5q]], [[3ey4]], [[3frj]], [[3hfg]], [[3fco]], [[3h6k]], [[3oq1]], [[3pdj]], [[3tfq]], [[3qqp]] - hHSD (mutant) + inhibitor + NADP<BR />
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| '''17-β HSD'''
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| [[1bhs]] – hHSD <BR />
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| [[1s9c]] - hHSD (mutant) <BR />
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| [[3is3]] – ClHSD – ''Cochliobolus lunatus''<BR />
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| [[3itd]] - ClHSD (mutant)
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| ''17-β HSD binary complex''
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| [[3qwf]] - ClHSD + NADP<BR />
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| [[1fdw]], [[1dht]] - hHSD (mutant) + hydroxysteroid<BR />
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| [[1jtv]], [[1yb1]], [[1dhe]], [[1fds]], [[1iol]], [[3klm]], [[3klp]], [[3km0]] - hHSD + hydroxysteroid
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| [[1fdv]] - hHSD (mutant) + NAD<BR />
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| [[1zbq]] - hHSD + NAD<BR />
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| [[1qyv]] - hHSD + NADP<BR />
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| [[1i5r]], [[1zq5]] - hHSD + inhibitor
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| ''17-β HSD ternary complex''
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| [[1qyw]], [[1qyx]], [[1xf0]], [[1fdt]] - hHSD + hydroxysteroid + NADP<BR />
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| [[1a27]], [[1fdu]] - hHSD (mutant) + hydroxysteroid + NADP<BR />
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| [[3hb5]], [[3r43]], [[3r58]], [[4dbs]], [[4dbu]], [[3uwe]] - hHSD + inhibitor + NADP<BR />
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| [[3qwi]], [[3qwh]] - ClHSD + hydroxysteroid + NADP<BR />
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| '''3-α 20-β HSD'''
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| [[2hsd]] – SeHSD – ''Streptomyces exfoliates''<BR />
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| [[1hdc]] – SeHSD + inhibitor | |
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| '''3-β/17-β HSD'''
| | </StructureSection> |
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| [[1hxh ]] - CtHSD | | == References == |
| | <references/> |
| | [[Category:Topic Page]] |
