Carboxymethylenebutenolidase Homolog (CMBL)

Carboxymethylenebutenolidase (CMBL), also known as 4-carboxymethylenebut-2-en-4-olide lactonohydrolase, maleylacetate enol- lactonase, dienelactone hydrolase, and carboxymethylene butenolide hydrolase, is a hydrolase specially belonging to the family of hydrolases. It maily acts on carboxylic ester bonds. CMBL is a human homolog of Pseudomonas dienelactone hydrolase involved in the bacterial halocatechol degradation pathway. The ubiquitous expression of human CMBL gene transcript in various tissues was observed. CMBL was demonstrated to be the primary olmesartan medoxomil (OM) bioactivating enzyme in the liver and intestine. The recombinant human CMBL expressed in mammalian cells was clearly shown to activate OM. The recombinant CMBL also converted other prodrugs having the same ester structure as OM, faropenem medoxomil and lenampicillin, to their active metabolites. CMBL exhibited a unique sensitivity to chemical inhibitors, thus, being distinguishable from other known esterases.

Carboxymethylenebutenolidase Homolog (CMBL) Related Areas

 

Carboxymethylenebutenolidase Homolog (CMBL) Alternative Names

FLJ23617 [Homo sapiens]

2310016A09Rik [Mus musculus]

Summaries for Carboxymethylenebutenolidase Homolog (CMBL)

OMIM - description for CMBL:

CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase family that is highly expressed in liver cytosol. CMBL preferentially cleaves cyclic esters, and it activates medoxomil-ester prodrugs in which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al., 2010).

Human Carboxymethylenebutenolidase Homolog (CMBL) Protein General Information

 

• Protein names: Carboxymethylenebutenolidase homolog
• Sequence length: 245 AA.
• Sequence similarities: CMBL belongs to the dienelactone hydrolase family.
• Enzyme regulation: CMBL is strongly inhibited by p-chloromercuribenzoate (PCMB). CMBL is partially inhibited by bis-p-nitrophenylphosphate (BNPP). CMBL is not inhibited by DFP, PMSF, eserine or EDTA.
• Subcellular location: Cytoplasm › cytosol
• Tissue specificity: Widely expressed, with highest levels in liver, followed by kidney, small intestine and colon. Present in liver and intestine (at protein level).

General information above from UniProt

Function for Carboxymethylenebutenolidase Homolog (CMBL) Protein

UniProtKB:

Cysteine hydrolase. Carboxymethylenebutenolidase Homolog (CMBL) can convert the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmerstatan, an angiotensin receptor blocker, in liver and intestine. CMBL may also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin.

Genatlas:

• CMBL catalyzes the conversion of dienelactones to maleylacetate
• CMBL is involved in the utilization of chlorocatechol

Homology for human Carboxymethylenebutenolidase Homolog (CMBL)

• homolog to rattus Cmbl (84.5 pc)
• homolog to murine Cmbl (82.9 pc)