HCDR1_XANP2
ID HCDR1_XANP2 Reviewed; 250 AA.
AC Q56840; A7IPY3;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=2-(R)-hydroxypropyl-CoM dehydrogenase {ECO:0000303|PubMed:10411892};
DE Short=R-HPCDH {ECO:0000303|PubMed:11851420};
DE EC=1.1.1.268 {ECO:0000269|PubMed:10411892, ECO:0000269|PubMed:11851420, ECO:0000269|PubMed:15157110, ECO:0000269|PubMed:20302306};
DE AltName: Full=2-[(R)-2-hydroxypropylthio]ethanesulfonate dehydrogenase {ECO:0000303|PubMed:11851420};
DE AltName: Full=Aliphatic epoxide carboxylation component III;
DE AltName: Full=Epoxide carboxylase component III {ECO:0000303|PubMed:9405410};
DE AltName: Full=RHPCDH1 {ECO:0000303|PubMed:20302306};
GN Name=xecD1 {ECO:0000303|PubMed:20302306}; OrderedLocusNames=Xaut_4868;
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 [GENOMIC DNA].
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=7704278; DOI=10.1099/13500872-141-2-477;
RA Swaving J., Weijers C.A.G.M., van Ooyen A.J.J., de Bont J.A.M.;
RT "Complementation of Xanthobacter Py2 mutants in epoxyalkane degradation;
RT expression and nucleotide sequence of the complementing DNA fragment.";
RL Microbiology 141:477-484(1995).
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 2-11, FUNCTION, PATHWAY, AND SUBUNIT.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=9405410; DOI=10.1074/jbc.272.51.32121;
RA Allen J.R., Ensign S.A.;
RT "Purification to homogeneity and reconstitution of the individual
RT components of the epoxide carboxylase multiprotein enzyme complex from
RT Xanthobacter strain Py2.";
RL J. Biol. Chem. 272:32121-32128(1997).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBUNIT.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=10411892; DOI=10.1073/pnas.96.15.8432;
RA Allen J.R., Clark D.D., Krum J.G., Ensign S.A.;
RT "A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial
RT pathway of aliphatic epoxide carboxylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:8432-8437(1999).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, MUTAGENESIS OF SER-142; TYR-155 AND LYS-159, AND
RP ACTIVE SITES.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=11851420; DOI=10.1021/bi0118005;
RA Clark D.D., Ensign S.A.;
RT "Characterization of the 2-[(R)-2-hydroxypropylthio]ethanesulfonate
RT dehydrogenase from Xanthobacter strain Py2: product inhibition, pH
RT dependence of kinetic parameters, site-directed mutagenesis, rapid
RT equilibrium inhibition, and chemical modification.";
RL Biochemistry 41:2727-2740(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, AND
RP MUTAGENESIS OF ARG-152; ARG-179; ARG-196; ARG-203 AND ARG-209.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=15157110; DOI=10.1021/bi049783h;
RA Clark D.D., Boyd J.M., Ensign S.A.;
RT "The stereoselectivity and catalytic properties of Xanthobacter
RT autotrophicus 2-[(R)-2-Hydroxypropylthio]ethanesulfonate dehydrogenase are
RT controlled by interactions between C-terminal arginine residues and the
RT sulfonate of coenzyme M.";
RL Biochemistry 43:6763-6771(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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 [8]
RP ACTIVITY REGULATION.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=20551308; DOI=10.1074/jbc.m110.144410;
RA Boyd J.M., Clark D.D., Kofoed M.A., Ensign S.A.;
RT "Mechanism of inhibition of aliphatic epoxide carboxylation by the coenzyme
RT M analog 2-bromoethanesulfonate.";
RL J. Biol. Chem. 285:25232-25242(2010).
RN [9]
RP REVIEW.
RX PubMed=12524213; DOI=10.1146/annurev.biochem.72.121801.161820;
RA Ensign S.A., Allen J.R.;
RT "Aliphatic epoxide carboxylation.";
RL Annu. Rev. Biochem. 72:55-76(2003).
RN [10] {ECO:0007744|PDB:2CFC}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH 2-OXOPROPYL-COENZYME
RP M AND NAD, SUBUNIT, DOMAIN, AND ACTIVE SITES.
RC STRAIN=ATCC BAA-1158 / Py2;
RX PubMed=16846226; DOI=10.1021/bi0603569;
RA Krishnakumar A.M., Nocek B.P., Clark D.D., Ensign S.A., Peters J.W.;
RT "Structural basis for stereoselectivity in the (R)- and (S)-
RT hydroxypropylthioethanesulfonate dehydrogenases.";
RL Biochemistry 45:8831-8840(2006).
CC -!- FUNCTION: Involved in aliphatic epoxide carboxylation (PubMed:9405410,
CC PubMed:10411892, PubMed:11851420). Catalyzes the reversible oxidation
CC of (R)-2-hydroxypropyl-coenzyme M (R-HPC) to 2-oxopropyl-coenzyme M (2-
CC KPC) (PubMed:10411892, PubMed:11851420, PubMed:15157110,
CC PubMed:20302306). The enzyme is highly specific for the R enantiomers
CC (PubMed:10411892, PubMed:15157110, PubMed:20302306). In vitro can also
CC use achiral 2-propanol and short-chain (R)- and (S)-2-alkanols
CC (PubMed:15157110). {ECO:0000269|PubMed:10411892,
CC ECO:0000269|PubMed:11851420, ECO:0000269|PubMed:15157110,
CC ECO:0000269|PubMed:20302306, ECO:0000269|PubMed:9405410}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxypropyl-coenzyme M + NAD(+) = 2-oxopropyl-coenzyme
CC M + H(+) + NADH; Xref=Rhea:RHEA:13249, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57552, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58458; EC=1.1.1.268;
CC Evidence={ECO:0000269|PubMed:10411892, ECO:0000269|PubMed:11851420,
CC ECO:0000269|PubMed:15157110, ECO:0000269|PubMed:20302306};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13250;
CC Evidence={ECO:0000269|PubMed:10411892, ECO:0000269|PubMed:11851420,
CC ECO:0000269|PubMed:15157110, ECO:0000269|PubMed:20302306};
CC -!- ACTIVITY REGULATION: Inhibited by the arginine-specific modifiers 2,3-
CC butanedione and phenylglyoxal (PubMed:11851420). 2-(2-methyl-2-
CC hydroxypropylthio)ethanesulfonate (M-HPC), an achiral analog of both R-
CC HPC and S-HPC, and (2S)-2-hydroxypropyl-coenzyme M (S-HPC) are
CC competitive inhibitors (PubMed:11851420, PubMed:20302306). Inhibited
CC (at 70%) by the coenzyme M analog 2-bromoethanesulfonate (BES)
CC (PubMed:20551308). {ECO:0000269|PubMed:11851420,
CC ECO:0000269|PubMed:20302306, ECO:0000269|PubMed:20551308}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=105 uM for R-HPC (at pH 7.5) {ECO:0000269|PubMed:11851420};
CC KM=102 uM for R-HPC (at pH 7.5) {ECO:0000269|PubMed:15157110};
CC KM=96 uM for R-HPC {ECO:0000269|PubMed:20302306};
CC KM=100 uM for S-HPC (at pH 7.5) {ECO:0000269|PubMed:15157110};
CC KM=220 uM for S-HPC {ECO:0000269|PubMed:20302306};
CC KM=1726 mM for 2-propanol (at pH 7.5) {ECO:0000269|PubMed:15157110};
CC KM=328 mM for (R)-2-butanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=315 mM for (S)-2-butanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=220 mM for (R)-2-butanol {ECO:0000269|PubMed:20302306};
CC KM=350 mM for (S)-2-butanol {ECO:0000269|PubMed:20302306};
CC KM=20 mM for (R)-2-pentanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=153 mM for (S)-2-pentanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=4.6 mM for (R)-2-hexanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=2.64 mM for (R)-2-heptanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=1.08 mM for (R)-2-octanol (at pH 7.5)
CC {ECO:0000269|PubMed:15157110};
CC KM=457 uM for NAD(+) (at pH 7.5) {ECO:0000269|PubMed:11851420};
CC KM=92 uM for 2-KPC (at pH 7.5) {ECO:0000269|PubMed:11851420};
CC KM=68 uM for 2-KPC {ECO:0000269|PubMed:20302306};
CC KM=36.6 uM for NADH (at pH 7.5) {ECO:0000269|PubMed:11851420};
CC Vmax=54.7 umol/min/mg enzyme for RHPC oxidation (at pH 7.5)
CC {ECO:0000269|PubMed:11851420};
CC Vmax=51.9 umol/min/mg enzyme for 2-KPC reduction (at pH 7.5)
CC {ECO:0000269|PubMed:11851420};
CC Note=kcat is 25.8 sec(-1) for R-HPC oxidation (at pH 7.5). kcat is
CC 24.5 sec(-1) for 2-KPC reduction (at pH 7.5) (PubMed:11851420). kcat
CC is 26.8 sec(-1) with R-HPC as substrate. kcat is 0.044 sec(-1) with
CC S-HPC as substrate. kcat is 2.9 sec(-1) with 2-propanol as substrate.
CC kcat is 0.98 sec(-1) with (R)-2-butanol as substrate. kcat is 2.2
CC sec(-1) with (S)-2-butanol as substrate. kcat is 1.1 sec(-1) with
CC (R)-2-pentanol as substrate. kcat is 2.9 sec(-1) with (S)-2-pentanol
CC as substrate. kcat is 2.7 sec(-1) with (R)-2-hexanol as substrate.
CC kcat is 1.8 sec(-1) with (R)-2-heptanol as substrate. kcat is 1.7
CC sec(-1) with (R)-2-octanol as substrate (PubMed:15157110). kcat is 48
CC sec(-1) with R-HPC as substrate. kcat is 0.12 sec(-1) with S-HPC as
CC substrate. kcat is 29 sec(-1) with 2-KPC as substrate
CC (PubMed:20302306). {ECO:0000269|PubMed:11851420,
CC ECO:0000269|PubMed:15157110, ECO:0000269|PubMed:20302306};
CC -!- PATHWAY: Alkene metabolism; propylene degradation.
CC {ECO:0000269|PubMed:10411892, ECO:0000269|PubMed:9405410}.
CC -!- SUBUNIT: Homodimer in solution (PubMed:9405410, PubMed:11851420).
CC Homotetramer (PubMed:16846226). Component III of the aliphatic epoxide
CC carboxylation complex together with components I, II and IV
CC (PubMed:9405410, PubMed:10411892). {ECO:0000269|PubMed:10411892,
CC ECO:0000269|PubMed:11851420, ECO:0000269|PubMed:16846226,
CC ECO:0000269|PubMed:9405410}.
CC -!- INDUCTION: By aliphatic and chlorinated alkenes.
CC -!- DOMAIN: Interactions between the sulfonate of coenzyme M (CoM) and
CC specific arginine residues are key to the enantioselectivity and
CC catalytic efficiency of R-HPCDH (PubMed:15157110, PubMed:16846226). The
CC structure is stabilized by the interaction of the terminal carboxylates
CC of each subunit with divalent metal ions (PubMed:16846226).
CC {ECO:0000269|PubMed:15157110, ECO:0000269|PubMed:16846226}.
CC -!- MISCELLANEOUS: Enantioselectivity is dictated largely by differences in
CC kcat. {ECO:0000269|PubMed:20302306}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305|PubMed:11851420}.
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DR EMBL; X79863; CAA56244.1; -; Genomic_DNA.
DR EMBL; CP000782; ABS70079.1; -; Genomic_DNA.
DR PIR; S47054; S47054.
DR RefSeq; WP_011992983.1; NC_009717.1.
DR PDB; 2CFC; X-ray; 1.80 A; A/B/C/D=2-250.
DR PDBsum; 2CFC; -.
DR AlphaFoldDB; Q56840; -.
DR SMR; Q56840; -.
DR STRING; 78245.Xaut_4868; -.
DR EnsemblBacteria; ABS70079; ABS70079; Xaut_4868.
DR KEGG; xau:Xaut_4868; -.
DR eggNOG; COG1028; Bacteria.
DR HOGENOM; CLU_010194_1_0_5; -.
DR OMA; MGEATCH; -.
DR OrthoDB; 1356861at2; -.
DR PhylomeDB; Q56840; -.
DR BioCyc; MetaCyc:MON-13285; -.
DR BRENDA; 1.1.1.268; 1641.
DR UniPathway; UPA00776; -.
DR EvolutionaryTrace; Q56840; -.
DR Proteomes; UP000002417; Plasmid pXAUT01.
DR GO; GO:0050574; F:2-(R)-hydroxypropyl-CoM dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0042208; P:propylene catabolic process; IEA:UniProtKB-UniPathway.
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; Direct protein sequencing; NAD; Oxidoreductase; Plasmid;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9405410"
FT CHAIN 2..250
FT /note="2-(R)-hydroxypropyl-CoM dehydrogenase"
FT /id="PRO_0000054705"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:11851420,
FT ECO:0000305|PubMed:16846226"
FT BINDING 12..14
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT BINDING 33
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT BINDING 60..61
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT BINDING 87
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT BINDING 152
FT /ligand="2-oxopropyl-coenzyme M"
FT /ligand_id="ChEBI:CHEBI:57552"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT BINDING 188..192
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT BINDING 195..196
FT /ligand="2-oxopropyl-coenzyme M"
FT /ligand_id="ChEBI:CHEBI:57552"
FT /evidence="ECO:0000269|PubMed:16846226,
FT ECO:0007744|PDB:2CFC"
FT SITE 142
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305|PubMed:11851420,
FT ECO:0000305|PubMed:16846226"
FT SITE 159
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000305|PubMed:11851420,
FT ECO:0000305|PubMed:16846226"
FT MUTAGEN 142
FT /note="S->A: Retains weak activity. 120-fold decrease in
FT kcat."
FT /evidence="ECO:0000269|PubMed:11851420"
FT MUTAGEN 142
FT /note="S->C: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11851420"
FT MUTAGEN 152
FT /note="R->A: Almost loss of activity with the natural
FT substrate 2-KPC, but does not affect activity with 2-
FT butanone as substrate."
FT /evidence="ECO:0000269|PubMed:15157110"
FT MUTAGEN 155
FT /note="Y->E,F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11851420"
FT MUTAGEN 159
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11851420"
FT MUTAGEN 179
FT /note="R->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15157110"
FT MUTAGEN 196
FT /note="R->A: Almost loss of activity with the natural
FT substrate 2-KPC, but does not affect activity with 2-
FT butanone as substrate."
FT /evidence="ECO:0000269|PubMed:15157110"
FT MUTAGEN 203
FT /note="R->A: Slight decrease in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15157110"
FT MUTAGEN 209
FT /note="R->A: Does not affect catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:15157110"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:2CFC"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 13..24
FT /evidence="ECO:0007829|PDB:2CFC"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 36..46
FT /evidence="ECO:0007829|PDB:2CFC"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:2CFC"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 64..78
FT /evidence="ECO:0007829|PDB:2CFC"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 116..132
FT /evidence="ECO:0007829|PDB:2CFC"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 153..173
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:2CFC"
FT STRAND 178..185
FT /evidence="ECO:0007829|PDB:2CFC"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 194..197
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 200..207
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 218..229
FT /evidence="ECO:0007829|PDB:2CFC"
FT STRAND 240..244
FT /evidence="ECO:0007829|PDB:2CFC"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:2CFC"
SQ SEQUENCE 250 AA; 26143 MW; F43B8A86CD7C1ED2 CRC64;
MSRVAIVTGA SSGNGLAIAT RFLARGDRVA ALDLSAETLE ETARTHWHAY ADKVLRVRAD
VADEGDVNAA IAATMEQFGA IDVLVNNAGI TGNSEAGVLH TTPVEQFDKV MAVNVRGIFL
GCRAVLPHML LQGAGVIVNI ASVASLVAFP GRSAYTTSKG AVLQLTKSVA VDYAGSGIRC
NAVCPGMIET PMTQWRLDQP ELRDQVLARI PQKEIGTAAQ VADAVMFLAG EDATYVNGAA
LVMDGAYTAI
