HCDS3_XANP2
ID HCDS3_XANP2 Reviewed; 255 AA.
AC A7IQH5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=2-(S)-hydroxypropyl-CoM dehydrogenase 3 {ECO:0000305};
DE Short=S-HPCDH 3 {ECO:0000303|PubMed:23474457};
DE EC=1.1.1.269 {ECO:0000269|PubMed:20302306};
DE AltName: Full=2-[(S)-2-hydroxypropylthio]ethanesulfonate dehydrogenase 3 {ECO:0000305};
DE AltName: Full=Aliphatic epoxide carboxylation component IV;
DE AltName: Full=Epoxide carboxylase component IV;
DE AltName: Full=SHPCDH3 {ECO:0000303|PubMed:20302306};
GN Name=xecE3 {ECO:0000303|PubMed:20302306};
GN OrderedLocusNames=Xaut_5073 {ECO:0000312|EMBL:ABS70271.1};
OS Xanthobacter autotrophicus (strain ATCC BAA-1158 / Py2).
OG Plasmid pXAUT01.
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Xanthobacteraceae; Xanthobacter.
OX NCBI_TaxID=78245;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-1158 / Py2;
RG US DOE Joint Genome Institute;
RA Copeland A., Lucas S., Lapidus A., Barry K., Glavina del Rio T., Hammon N.,
RA Israni S., Dalin E., Tice H., Pitluck S., Sims D., Brettin T., Bruce D.,
RA Detter J.C., Han C., Tapia R., Brainard J., Schmutz J., Larimer F.,
RA Land M., Hauser L., Kyrpides N., Kim E., Ensigns S.A., Richardson P.;
RT "Complete sequence of plasmid pXAUT01 of Xanthobacter autotrophicus Py2.";
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF SER-143; TYR-156; LYS-160; ARG-211 AND LYS-214,
RP AND ACTIVE SITES.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=20302306; DOI=10.1021/bi100294m;
RA Sliwa D.A., Krishnakumar A.M., Peters J.W., Ensign S.A.;
RT "Molecular basis for enantioselectivity in the (R)- and (S)-
RT hydroxypropylthioethanesulfonate dehydrogenases, a unique pair of
RT stereoselective short-chain dehydrogenases/reductases involved in aliphatic
RT epoxide carboxylation.";
RL Biochemistry 49:3487-3498(2010).
RN [3] {ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH NAD AND
RP (S)-2-HYDROXYPROPYL-COENZYME M, SUBUNIT, AND ACTIVE SITES.
RX PubMed=23474457; DOI=10.1016/j.abb.2013.02.017;
RA Bakelar J.W., Sliwa D.A., Johnson S.J.;
RT "Crystal structures of S-HPCDH reveal determinants of stereospecificity for
RT R- and S-hydroxypropyl-coenzyme M dehydrogenases.";
RL Arch. Biochem. Biophys. 533:62-68(2013).
CC -!- FUNCTION: Involved in aliphatic epoxide carboxylation
CC (PubMed:20302306). Catalyzes the reversible oxidation of (2S)-2-
CC hydroxypropyl-coenzyme M (S-HPC) to 2-oxopropyl-coenzyme M (2-KPC)
CC (PubMed:20302306). The enzyme is highly specific for the S enantiomers
CC (PubMed:20302306). In vitro can also use the aliphatic ketone 2-
CC butanone and the aliphatic alcohol 2-propanol, and shows an inherent
CC stereoselectivity for 2-butanone reduction (PubMed:20302306).
CC {ECO:0000269|PubMed:20302306}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-hydroxypropyl-coenzyme M + NAD(+) = 2-oxopropyl-
CC coenzyme M + H(+) + NADH; Xref=Rhea:RHEA:21052, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57552, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58430; EC=1.1.1.269;
CC Evidence={ECO:0000269|PubMed:20302306};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21053;
CC Evidence={ECO:0000269|PubMed:20302306};
CC -!- ACTIVITY REGULATION: Not inhibited by 2-(2-methyl-2-
CC hydroxypropylthio)ethanesulfonate (M-HPC), an achiral analog of both R-
CC HPC and S-HPC. {ECO:0000269|PubMed:20302306}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=31 uM for S-HPC {ECO:0000269|PubMed:20302306};
CC KM=270 uM for 2-KPC {ECO:0000269|PubMed:20302306};
CC KM=9100 uM for R-HPC {ECO:0000269|PubMed:20302306};
CC KM=120 mM for 2-butanone {ECO:0000269|PubMed:20302306};
CC KM=1400 mM for 2-propanol {ECO:0000269|PubMed:20302306};
CC KM=68 mM for (R)-2-butanol {ECO:0000269|PubMed:20302306};
CC KM=28 mM for (S)-2-butanol {ECO:0000269|PubMed:20302306};
CC KM=191 uM for NAD(+) {ECO:0000269|PubMed:20302306};
CC KM=8.42 uM for NADH {ECO:0000269|PubMed:20302306};
CC Note=kcat is 5.5 sec(-1) with R-HPC as substrate. kcat is 25 sec(-1)
CC with S-HPC as substrate. kcat is 11 sec(-1) with 2-KPC as substrate.
CC kcat is 0.044 sec(-1) with 2-butanone as substrate. kcat is 2.0 sec(-
CC 1) with 2-propanol as substrate. kcat is 1.0 sec(-1) with (R)-2-
CC butanol as substrate. kcat is 2.6 sec(-1) with (S)-2-butanol as
CC substrate. {ECO:0000269|PubMed:20302306};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:23474457}.
CC -!- MISCELLANEOUS: Enantioselectivity is dictated largely by changes in Km.
CC {ECO:0000269|PubMed:20302306}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP000782; ABS70271.1; -; Genomic_DNA.
DR RefSeq; WP_011993174.1; NC_009717.1.
DR PDB; 4GH5; X-ray; 1.60 A; A/B/C/D=1-255.
DR PDB; 4ITU; X-ray; 1.60 A; A/B/C/D=1-255.
DR PDBsum; 4GH5; -.
DR PDBsum; 4ITU; -.
DR SMR; A7IQH5; -.
DR STRING; 78245.Xaut_5073; -.
DR EnsemblBacteria; ABS70271; ABS70271; Xaut_5073.
DR KEGG; xau:Xaut_5073; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_2_5; -.
DR OMA; VNICTEG; -.
DR OrthoDB; 1356861at2; -.
DR PhylomeDB; A7IQH5; -.
DR BRENDA; 1.1.1.269; 1641.
DR Proteomes; UP000002417; Plasmid pXAUT01.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; NAD; Nucleotide-binding; Oxidoreductase; Plasmid;
KW Reference proteome.
FT CHAIN 1..255
FT /note="2-(S)-hydroxypropyl-CoM dehydrogenase 3"
FT /id="PRO_0000454346"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:20302306,
FT ECO:0000305|PubMed:23474457"
FT BINDING 19
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU"
FT BINDING 38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU"
FT BINDING 64..65
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU"
FT BINDING 91
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU"
FT BINDING 143
FT /ligand="(2S)-2-hydroxypropyl-coenzyme M"
FT /ligand_id="ChEBI:CHEBI:58430"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4ITU"
FT BINDING 156
FT /ligand="(2S)-2-hydroxypropyl-coenzyme M"
FT /ligand_id="ChEBI:CHEBI:58430"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4ITU"
FT BINDING 160
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU"
FT BINDING 188
FT /ligand="(2S)-2-hydroxypropyl-coenzyme M"
FT /ligand_id="ChEBI:CHEBI:58430"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4ITU"
FT BINDING 189..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4GH5, ECO:0007744|PDB:4ITU"
FT BINDING 215
FT /ligand="(2S)-2-hydroxypropyl-coenzyme M"
FT /ligand_id="ChEBI:CHEBI:58430"
FT /evidence="ECO:0000269|PubMed:23474457,
FT ECO:0007744|PDB:4ITU"
FT SITE 143
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305|PubMed:20302306,
FT ECO:0000305|PubMed:23474457"
FT SITE 160
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000305|PubMed:20302306,
FT ECO:0000305|PubMed:23474457"
FT MUTAGEN 143
FT /note="S->A: Retains very weak activity."
FT /evidence="ECO:0000269|PubMed:20302306"
FT MUTAGEN 156
FT /note="Y->A: Retains some activity but with more than 2200-
FT fold decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:20302306"
FT MUTAGEN 156
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:20302306"
FT MUTAGEN 160
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:20302306"
FT MUTAGEN 211
FT /note="R->A: Severely impaired in the oxidation of S-HPC or
FT reduction of 2-KPC but largely unaffected in the oxidation
FT and reduction of aliphatic alcohols and ketones."
FT /evidence="ECO:0000269|PubMed:20302306"
FT MUTAGEN 214
FT /note="K->A: Severely impaired in the oxidation of S-HPC or
FT reduction of 2-KPC but largely unaffected in the oxidation
FT and reduction of aliphatic alcohols and ketones."
FT /evidence="ECO:0000269|PubMed:20302306"
FT TURN 4..7
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:4GH5"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 41..51
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 68..82
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:4GH5"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 105..132
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 136..141
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 154..174
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 179..186
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 193..197
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 206..212
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 223..234
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:4GH5"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:4GH5"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4GH5"
SQ SEQUENCE 255 AA; 25473 MW; 12E8F086584059B5 CRC64;
MSNRLKNEVI AITGGGAGIG LAIASAALRE GAKVALIDLD QGLAERSAAM LSTGGAVAKG
FGADVTKAAD ITAAITSAEQ TIGSLTGLVN NAGIAGFGSV HDADAAAWDR IMAVNVTGTF
LASKAALAGM LERHKGTIVN FGSVAGLVGI PTMAAYCAAK GAIVNLTRQM AADYSGRGVR
VNAVCPGTVT STGMGQQLLG SDTSPEVQAR RLAKYPIGRF GTPEDIAEAV IFLLSDQAAF
VTGAAFAVDG GMTAI
