HCMB_AQUTE
ID HCMB_AQUTE Reviewed; 136 AA.
AC I3VE74;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=2-hydroxyisobutanoyl-CoA mutase small subunit {ECO:0000305};
DE EC=5.4.99.64 {ECO:0000269|PubMed:22433853, ECO:0000269|PubMed:25720495};
DE AltName: Full=2-hydroxyisobutyryl-CoA mutase small subunit {ECO:0000303|PubMed:22433853};
DE Short=HCM small subunit {ECO:0000303|PubMed:22433853};
GN Name=hcmB {ECO:0000303|PubMed:22433853};
OS Aquincola tertiaricarbonis.
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; Aquincola.
OX NCBI_TaxID=391953;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND DISRUPTION PHENOTYPE.
RC STRAIN=L108;
RX PubMed=22433853; DOI=10.1074/jbc.m111.314690;
RA Yaneva N., Schuster J., Schafer F., Lede V., Przybylski D., Paproth T.,
RA Harms H., Muller R.H., Rohwerder T.;
RT "Bacterial acyl-CoA mutase specifically catalyzes coenzyme B12-dependent
RT isomerization of 2-hydroxyisobutyryl-CoA and (S)-3-hydroxybutyryl-CoA.";
RL J. Biol. Chem. 287:15502-15511(2012).
RN [2] {ECO:0007744|PDB:4R3U}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH HCMA;
RP 2-HYDROXYISOBUTANOYL-COA; 3-HYDROXYBUTANOYL-COA AND COBALAMIN, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC STRAIN=L108;
RX PubMed=25720495; DOI=10.1074/jbc.m115.645689;
RA Kurteva-Yaneva N., Zahn M., Weichler M.T., Starke R., Harms H.,
RA Muller R.H., Strater N., Rohwerder T.;
RT "Structural basis of the stereospecificity of bacterial B12-dependent 2-
RT hydroxyisobutyryl-CoA mutase.";
RL J. Biol. Chem. 290:9727-9737(2015).
CC -!- FUNCTION: Together with HcmA, catalyzes the isomerization of 2-
CC hydroxyisobutyryl-CoA and 3-hydroxybutyryl-CoA. Is specific for 2-
CC hydroxyisobutyryl-CoA and (S)-3-hydroxybutyryl-CoA, and shows only very
CC low activity with (R)-3-hydroxybutyryl-CoA, isobutyryl-CoA and butyryl-
CC CoA (PubMed:22433853, PubMed:25720495). In vitro, can isomerize
CC pivalyl-CoA and isovaleryl-CoA, with much lower efficiency
CC (PubMed:25720495). Plays a central role in the degradation of
CC substrates bearing a tert-butyl moiety, such as the fuel oxygenate
CC methyl tert-butyl ether (MTBE) and its metabolites (PubMed:22433853).
CC {ECO:0000269|PubMed:22433853, ECO:0000269|PubMed:25720495}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyisobutanoyl-CoA = (3S)-3-hydroxybutanoyl-CoA;
CC Xref=Rhea:RHEA:49592, ChEBI:CHEBI:57316, ChEBI:CHEBI:131780;
CC EC=5.4.99.64; Evidence={ECO:0000269|PubMed:22433853,
CC ECO:0000269|PubMed:25720495};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49593;
CC Evidence={ECO:0000269|PubMed:22433853};
CC -!- COFACTOR:
CC Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408;
CC Evidence={ECO:0000269|PubMed:25720495};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=128 uM for (S)-3-hydroxybutyryl-CoA {ECO:0000269|PubMed:22433853};
CC KM=104 uM for 2-hydroxyisobutyryl-CoA {ECO:0000269|PubMed:22433853};
CC KM=1660 uM for (R)-3-hydroxybutyryl-CoA
CC {ECO:0000269|PubMed:22433853};
CC KM=3340 uM for butyryl-CoA {ECO:0000269|PubMed:22433853};
CC KM=550 uM for isobutyryl-CoA {ECO:0000269|PubMed:22433853};
CC KM=374 uM for pivalyl-CoA {ECO:0000269|PubMed:25720495};
CC KM=288 uM for isovaleryl-CoA {ECO:0000269|PubMed:25720495};
CC Vmax=140 nmol/min/mg enzyme with (S)-3-hydroxybutyryl-CoA as
CC substrate {ECO:0000269|PubMed:22433853};
CC Vmax=36 nmol/min/mg enzyme with 2-hydroxyisobutyryl-CoA as substrate
CC {ECO:0000269|PubMed:22433853};
CC Vmax=2.4 nmol/min/mg enzyme with (R)-3-hydroxybutyryl-CoA as
CC substrate {ECO:0000269|PubMed:22433853};
CC Vmax=2.4 nmol/min/mg enzyme with butyryl-CoA as substrate
CC {ECO:0000269|PubMed:22433853};
CC Vmax=0.67 nmol/min/mg enzyme with isobutyryl-CoA as substrate
CC {ECO:0000269|PubMed:22433853};
CC Vmax=11.8 nmol/min/mg enzyme with pivalyl-CoA as substrate
CC {ECO:0000269|PubMed:25720495};
CC Vmax=8.2 nmol/min/mg enzyme with isovaleryl-CoA as substrate
CC {ECO:0000269|PubMed:25720495};
CC Note=kcat is 12 min(-1) with (S)-3-hydroxybutyryl-CoA as substrate.
CC kcat is 3.0 min(-1) with 2-hydroxyisobutyryl-CoA as substrate. kcat
CC is 0.20 min(-1) with (R)-3-hydroxybutyryl-CoA as substrate. kcat is
CC 0.20 min(-1) with butyryl-CoA as substrate. kcat is 0.06 min(-1) with
CC isobutyryl-CoA as substrate (PubMed:22433853). kcat is 0.98 min(-1)
CC with pivalyl-CoA as substrate. kcat is 0.68 min(-1) with isovaleryl-
CC CoA as substrate (PubMed:25720495). {ECO:0000269|PubMed:22433853,
CC ECO:0000269|PubMed:25720495};
CC pH dependence:
CC Optimum pH is 6.6. {ECO:0000269|PubMed:22433853};
CC Temperature dependence:
CC Optimum temperature is 30 degrees Celsius.
CC {ECO:0000269|PubMed:22433853};
CC -!- SUBUNIT: Homotetramer composed of two large substrate-binding subunits
CC (HcmA) and two small cobalamin-binding subunits (HcmB).
CC {ECO:0000269|PubMed:22433853, ECO:0000269|PubMed:25720495}.
CC -!- DISRUPTION PHENOTYPE: Insertion mutant cannot grow on 2-
CC hydroxyisobutyric acid (2-HIBA). {ECO:0000269|PubMed:22433853}.
CC -!- SIMILARITY: Belongs to the acyl-CoA mutase small subunit family.
CC {ECO:0000305}.
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DR EMBL; JQ708092; AFK77665.1; -; Genomic_DNA.
DR PDB; 4R3U; X-ray; 2.50 A; C/D=1-136.
DR PDBsum; 4R3U; -.
DR SMR; I3VE74; -.
DR KEGG; ag:AFK77665; -.
DR BioCyc; MetaCyc:MON-19835; -.
DR BRENDA; 5.4.99.64; 14508.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR006159; Acid_CoA_mut_C.
DR InterPro; IPR006158; Cobalamin-bd.
DR InterPro; IPR036724; Cobalamin-bd_sf.
DR Pfam; PF02310; B12-binding; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR TIGRFAMs; TIGR00640; acid_CoA_mut_C; 1.
DR PROSITE; PS51332; B12_BINDING; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cobalamin; Cobalt; Isomerase; Metal-binding.
FT CHAIN 1..136
FT /note="2-hydroxyisobutanoyl-CoA mutase small subunit"
FT /id="PRO_0000455119"
FT DOMAIN 5..133
FT /note="B12-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT BINDING 18
FT /ligand="adenosylcob(III)alamin"
FT /ligand_id="ChEBI:CHEBI:18408"
FT /ligand_part="Co"
FT /ligand_part_id="ChEBI:CHEBI:27638"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:25720495,
FT ECO:0007744|PDB:4R3U"
SQ SEQUENCE 136 AA; 14515 MW; 21719798776ED1EC CRC64;
MDQTPIRVLL AKVGLDGHDR GVKVVARALR DAGMDVIYSG LHRTPEEVVN TAIQEDVDVL
GVSLLSGVQL TVFPKIFKLL DERGAGDLIV IAGGVMPDED AAAIRKLGVR EVLLQDTPPQ
AIIDSIRSLV AARGAR
