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| | <StructureSection load='5fyd' size='340' side='right'caption='[[5fyd]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='5fyd' size='340' side='right'caption='[[5fyd]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fyd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacteroides_aerofaciens"_eggerth_1935 "bacteroides aerofaciens" eggerth 1935]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FYD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FYD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fyd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Collinsella_aerofaciens Collinsella aerofaciens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FYD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FYD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.6Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/7-beta-hydroxysteroid_dehydrogenase_(NADP(+)) 7-beta-hydroxysteroid dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.201 1.1.1.201] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5fyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fyd OCA], [http://pdbe.org/5fyd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fyd RCSB], [http://www.ebi.ac.uk/pdbsum/5fyd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fyd ProSAT]</span></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=5fyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fyd OCA], [https://pdbe.org/5fyd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fyd RCSB], [https://www.ebi.ac.uk/pdbsum/5fyd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fyd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HSDHB_COLAA HSDHB_COLAA] 7beta-hydroxysteroid dehydrogenase that catalyzes the reduction of the 7-oxo group of 7-oxo-lithocholate (7-oxo-LCA), to yield ursodeoxycholate (UDCA) (PubMed:21181147, PubMed:6954878, PubMed:27006087). As C.aerofaciens is an intestinal bacterium, this enzyme probably contributes to the formation of UDCA in the human colon. UDCA is regarded as a chemopreventive beneficial secondary bile acid due to its low hydrophobicity; it protects hepatocytes and bile duct epithelial cells against necrosis and apoptosis induced by more hydrophobic secondary bile acids like deoxycholate (DCA) (Probable). This enzyme is also able to catalyze the reverse reaction, i.e. the oxidation of the 7beta-hydroxy group of UDCA to 7-oxo-LCA (PubMed:21181147, PubMed:6954878). To a lesser extent, is also active on the taurine- and glycine-conjugates of ursodeoxycholate. It is specific for NADPH/NADP(+) as the electron acceptor/donor since it is not active with NADH/NAD(+) (PubMed:6954878). In the presence of NADPH, 7beta-HSDH can also reduce dehydrocholate (PubMed:21181147). And is also able to oxidize ursocholate (PubMed:27006087).<ref>PMID:21181147</ref> <ref>PMID:27006087</ref> <ref>PMID:6954878</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5fyd" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5fyd" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacteroides aerofaciens eggerth 1935]] | + | [[Category: Collinsella aerofaciens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ferrandi, E]] | + | [[Category: Ferrandi E]] |
| - | [[Category: Forneris, F]] | + | [[Category: Forneris F]] |
| - | [[Category: Mattevi, A]] | + | [[Category: Mattevi A]] |
| - | [[Category: Monti, D]] | + | [[Category: Monti D]] |
| - | [[Category: Riva, S]] | + | [[Category: Riva S]] |
| - | [[Category: Rovida, S]] | + | [[Category: Rovida S]] |
| - | [[Category: Savino, S]] | + | [[Category: Savino S]] |
| - | [[Category: Dehydrogenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Short-chain dehydrogenase]]
| + | |
| - | [[Category: Stereoselectivity]]
| + | |
| - | [[Category: Steroid]]
| + | |
| Structural highlights
Function
HSDHB_COLAA 7beta-hydroxysteroid dehydrogenase that catalyzes the reduction of the 7-oxo group of 7-oxo-lithocholate (7-oxo-LCA), to yield ursodeoxycholate (UDCA) (PubMed:21181147, PubMed:6954878, PubMed:27006087). As C.aerofaciens is an intestinal bacterium, this enzyme probably contributes to the formation of UDCA in the human colon. UDCA is regarded as a chemopreventive beneficial secondary bile acid due to its low hydrophobicity; it protects hepatocytes and bile duct epithelial cells against necrosis and apoptosis induced by more hydrophobic secondary bile acids like deoxycholate (DCA) (Probable). This enzyme is also able to catalyze the reverse reaction, i.e. the oxidation of the 7beta-hydroxy group of UDCA to 7-oxo-LCA (PubMed:21181147, PubMed:6954878). To a lesser extent, is also active on the taurine- and glycine-conjugates of ursodeoxycholate. It is specific for NADPH/NADP(+) as the electron acceptor/donor since it is not active with NADH/NAD(+) (PubMed:6954878). In the presence of NADPH, 7beta-HSDH can also reduce dehydrocholate (PubMed:21181147). And is also able to oxidize ursocholate (PubMed:27006087).[1] [2] [3]
Publication Abstract from PubMed
Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo- and regio-selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7beta-hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active-site accessibility, the bases of the specificity for NADP+ , and the general architecture of the steroid binding site. Comparison with 7alpha-hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C-terminal extension reshapes the substrate site of the beta-selective enzyme, possibly leading to an inverted orientation of the bound substrate. This article is protected by copyright. All rights reserved.
Structural and biochemical insights into 7beta-hydroxysteroid dehydrogenase stereoselectivity.,Savino S, Ferrandi EE, Forneris F, Rovida S, Riva S, Monti D, Mattevi A Proteins. 2016 Mar 23. doi: 10.1002/prot.25036. PMID:27006087[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu L, Aigner A, Schmid RD. Identification, cloning, heterologous expression, and characterization of a NADPH-dependent 7β-hydroxysteroid dehydrogenase from Collinsella aerofaciens. Appl Microbiol Biotechnol. 2011 Apr;90(1):127-35. PMID:21181147 doi:10.1007/s00253-010-3052-y
- ↑ Savino S, Ferrandi EE, Forneris F, Rovida S, Riva S, Monti D, Mattevi A. Structural and biochemical insights into 7beta-hydroxysteroid dehydrogenase stereoselectivity. Proteins. 2016 Mar 23. doi: 10.1002/prot.25036. PMID:27006087 doi:http://dx.doi.org/10.1002/prot.25036
- ↑ Hirano S, Masuda N. Characterization of NADP-dependent 7 beta-hydroxysteroid dehydrogenases from Peptostreptococcus productus and Eubacterium aerofaciens. Appl Environ Microbiol. 1982 May;43(5):1057-63. PMID:6954878 doi:10.1128/aem.43.5.1057-1063.1982
- ↑ Savino S, Ferrandi EE, Forneris F, Rovida S, Riva S, Monti D, Mattevi A. Structural and biochemical insights into 7beta-hydroxysteroid dehydrogenase stereoselectivity. Proteins. 2016 Mar 23. doi: 10.1002/prot.25036. PMID:27006087 doi:http://dx.doi.org/10.1002/prot.25036
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