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Overview for MACiE Entry M0345

Version history

General Information

EC Number: 3.1.2.4 (A member of the Hydrolases, Acting on ester bonds, Thioester hydrolases)

Enzyme Name: 3-hydroxyisobutyryl-CoA hydrolase

Biological Species: Homo sapiens (Human)

Catalytic Chain UniprotKB Accession Codes:

  • Q6NVY1 - 3-hydroxyisobutyryl-CoA hydrolase, mitochondrial

Representative PDB Code: 3bpt - CRYSTAL STRUCTURE OF HUMAN BETA-HYDROXYISOBUTYRYL-COA HYDROLASE INCOMPLEX WITH QUERCETIN (Resolution = 1.50 Å).

Catalytic CATH Codes:

  • Unassigned Domain

Display structure information

Overall Reaction:

Image of water

Image of 3-hydroxy-2-methylpropanoyl-CoA

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Image of 3-hydroxy-2-methylpropanoate

Image of CoA

water
C00001
CHEBI:15377
3-hydroxy-2-methylpropanoyl-CoA
C04047
CHEBI:57340
3-hydroxy-2-methylpropanoate
C01188
CHEBI:18064
CoA
C00010
CHEBI:57288

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Stepwise Description of the Reaction

Step 1Glu169 nucleophilicly attacks the carboxylate group on the substrate to generate an anhydride intermediate. This is facilitated by the binding of the thioester oxygen atom to an oxyanion hole formed by the peptide nitrogens of Gly98 and of Gly146.
Step 2The anhydride intermediate undergoes internal elimination to produce CoA and an intermediate.
Step 3A water molecule, activated by Asp177A, attacks the carbonyl carbon of the covalently attached Glu169A.
Step 4The final intermediate undergoes internal elimination to liberate the Glu169A and producing 3-hydroxy-2-methylpropanoate.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Gly 98 A Main Chain Amide
Gly 146 A Main Chain Amide
Glu 169 A Side Chain
Asp 177 A Side Chain

References

  1. B.K. Zolman et al. (2001), J. Biol. Chem., 276, 31037-31046. chy1, an Arabidopsis mutant with impaired beta-oxidation, is defective in a peroxisomal beta-hydroxyisobutyryl-CoA hydrolase.
    Medline: 11404361
  2. B.J. Wong et al. (2003), J. Am. Chem. Soc., 125, 12076-12077. Divergent function in the crotonase superfamily: an anhydride intermediate in the reaction catalyzed by 3-hydroxyisobutyryl-CoA hydrolase.
    Medline: 14518977

Homologue information for M0345 (3bpt)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

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catalytic activity (molecular function)
3-hydroxyisobutyryl-CoA hydrolase activity (molecular function)
protein binding (molecular function)
mitochondrion (cellular component)
mitochondrial matrix (cellular component)
metabolic process (biological process)
branched-chain amino acid catabolic process (biological process)
hydrolase activity (molecular function)
cellular nitrogen compound metabolic process (biological process)
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