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| - | ==STRUCTURAL BASIS FOR STEREO SELECTIVITY IN THE (R)- AND (S)-HYDROXYPROPYLETHANE THIOSULFONATE DEHYDROGENASES== | + | |
| - | <StructureSection load='2cfc' size='340' side='right' caption='[[2cfc]], [[Resolution|resolution]] 1.80Å' scene=''> | + | ==structural basis for stereo selectivity in the (R)- and (S)- hydroxypropylethane thiosulfonate dehydrogenases== |
| | + | <StructureSection load='2cfc' size='340' side='right'caption='[[2cfc]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cfc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Xanthobacter_autotrophicus Xanthobacter autotrophicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CFC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CFC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cfc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Xanthobacter_autotrophicus_Py2 Xanthobacter autotrophicus Py2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CFC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KPC:(2-[2-KETOPROPYLTHIO]ETHANESULFONATE'>KPC</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 1.8Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-(R)-hydroxypropyl-CoM_dehydrogenase 2-(R)-hydroxypropyl-CoM dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.268 1.1.1.268] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KPC:(2-[2-KETOPROPYLTHIO]ETHANESULFONATE'>KPC</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></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=2cfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cfc OCA], [http://pdbe.org/2cfc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cfc RCSB], [http://www.ebi.ac.uk/pdbsum/2cfc PDBsum]</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=2cfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cfc OCA], [https://pdbe.org/2cfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cfc RCSB], [https://www.ebi.ac.uk/pdbsum/2cfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cfc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HCDR1_XANP2 HCDR1_XANP2] Involved in aliphatic epoxide carboxylation (PubMed:9405410, PubMed:10411892, PubMed:11851420). Catalyzes the reversible oxidation of (R)-2-hydroxypropyl-coenzyme M (R-HPC) to 2-oxopropyl-coenzyme M (2-KPC) (PubMed:10411892, PubMed:11851420, PubMed:15157110, PubMed:20302306). The enzyme is highly specific for the R enantiomers (PubMed:10411892, PubMed:15157110, PubMed:20302306). In vitro can also use achiral 2-propanol and short-chain (R)- and (S)-2-alkanols (PubMed:15157110).<ref>PMID:10411892</ref> <ref>PMID:11851420</ref> <ref>PMID:15157110</ref> <ref>PMID:20302306</ref> <ref>PMID:9405410</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cf/2cfc_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cf/2cfc_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cfc ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Xanthobacter autotrophicus]] | + | [[Category: Large Structures]] |
| - | [[Category: Clark, D D]] | + | [[Category: Xanthobacter autotrophicus Py2]] |
| - | [[Category: Ensign, S A]] | + | [[Category: Clark DD]] |
| - | [[Category: Krishnakumar, A M]] | + | [[Category: Ensign SA]] |
| - | [[Category: Nocek, B P]] | + | [[Category: Krishnakumar AM]] |
| - | [[Category: Peters, J W]] | + | [[Category: Nocek BP]] |
| - | [[Category: Nad]]
| + | [[Category: Peters JW]] |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
HCDR1_XANP2 Involved in aliphatic epoxide carboxylation (PubMed:9405410, PubMed:10411892, PubMed:11851420). Catalyzes the reversible oxidation of (R)-2-hydroxypropyl-coenzyme M (R-HPC) to 2-oxopropyl-coenzyme M (2-KPC) (PubMed:10411892, PubMed:11851420, PubMed:15157110, PubMed:20302306). The enzyme is highly specific for the R enantiomers (PubMed:10411892, PubMed:15157110, PubMed:20302306). In vitro can also use achiral 2-propanol and short-chain (R)- and (S)-2-alkanols (PubMed:15157110).[1] [2] [3] [4] [5]
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
Epoxide metabolism in Xanthobacter autotrophicus Py2 results in the conversion of epoxypropane to acetoacetate. Epoxide metabolism is initiated by the nucleophilic addition of coenzyme M to the (R)- and (S)-enantiomers of epoxypropane which forms the respective enantiomers of 2-hydroxypropyl-coenyme M. The (R)- and (S)-enantiomers of 2-hydroxypropyl coenzyme are oxidized to the achiral product 2-ketopropyl-CoM by two stereoselective dehydrogenases. The dehydrogenases catalyzing these reactions, termed (R)-hydroxypropyl-coenzyme M dehydrogenase (R-HPCDH) and (S)-hydroxypropyl-coenzyme M dehydrogenase (S-HPCDH), are NAD(+)-dependent enzymes belonging to the short chain dehydrogenase/reductase (SDR) family of enzymes. In this study, the crystal structure of R-HPCDH cocrystallized in the presence of (S)-hydroxypropyl-coenzyme M has been determined using X-ray diffraction methods and refined to 1.8 A resolution. The structure of R-HPCDH is tetrameric and stabilized by the interaction of the terminal carboxylates of each subunit with divalent metal ions. The structure of the presumed product-bound state reveals that binding interactions between the negatively charged oxygen atoms of the sulfonate moiety have striking similarities to sulfonate interactions observed in the previously determined structure of 2-ketopropyl-CoM oxidoreductase/carboxylase, highlighting the utility of coenzyme M as a carrier molecule in the pathway. The key elements of the aforementioned interactions are electrostatic interactions between the sulfonate oxygen atoms and two arginine residues (R152 and R196) of R-HPCDH. The comparison of the structure of R-HPCDH with a homology model of S-HPCDH provides a structural basis for a mechanism of substrate specificity in which the binding of the substrate sulfonate moiety at distinct sites on each stereoselective enzyme directs the orientation of the appropriate substrate enantiomer for hydride abstraction.
Structural basis for stereoselectivity in the (R)- and (S)-hydroxypropylthioethanesulfonate dehydrogenases.,Krishnakumar AM, Nocek BP, Clark DD, Ensign SA, Peters JW Biochemistry. 2006 Jul 25;45(29):8831-40. PMID:16846226[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Allen JR, Clark DD, Krum JG, Ensign SA. A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial pathway of aliphatic epoxide carboxylation. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8432-7. PMID:10411892 doi:10.1073/pnas.96.15.8432
- ↑ Clark DD, Ensign SA. Characterization of the 2-[(R)-2-hydroxypropylthio]ethanesulfonate dehydrogenase from Xanthobacter strain Py2: product inhibition, pH dependence of kinetic parameters, site-directed mutagenesis, rapid equilibrium inhibition, and chemical modification. Biochemistry. 2002 Feb 26;41(8):2727-40. PMID:11851420 doi:10.1021/bi0118005
- ↑ Clark DD, Boyd JM, Ensign SA. The stereoselectivity and catalytic properties of Xanthobacter autotrophicus 2-[(R)-2-Hydroxypropylthio]ethanesulfonate dehydrogenase are controlled by interactions between C-terminal arginine residues and the sulfonate of coenzyme M. Biochemistry. 2004 Jun 1;43(21):6763-71. PMID:15157110 doi:10.1021/bi049783h
- ↑ Sliwa DA, Krishnakumar AM, Peters JW, Ensign SA. Molecular basis for enantioselectivity in the (R)- and (S)-hydroxypropylthioethanesulfonate dehydrogenases, a unique pair of stereoselective short-chain dehydrogenases/reductases involved in aliphatic epoxide carboxylation. Biochemistry. 2010 Apr 27;49(16):3487-98. doi: 10.1021/bi100294m. PMID:20302306 doi:http://dx.doi.org/10.1021/bi100294m
- ↑ Allen JR, Ensign SA. Purification to homogeneity and reconstitution of the individual components of the epoxide carboxylase multiprotein enzyme complex from Xanthobacter strain Py2. J Biol Chem. 1997 Dec 19;272(51):32121-8. PMID:9405410 doi:10.1074/jbc.272.51.32121
- ↑ Krishnakumar AM, Nocek BP, Clark DD, Ensign SA, Peters JW. Structural basis for stereoselectivity in the (R)- and (S)-hydroxypropylthioethanesulfonate dehydrogenases. Biochemistry. 2006 Jul 25;45(29):8831-40. PMID:16846226 doi:10.1021/bi0603569
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