CMBL Human

CMBL catalyzes the hydrolysis of 4-carboxymethylenebut-2-en-4-olide to produce 4-oxohex-2-enedioate . This reaction involves the addition of a water molecule (H₂O) to the substrate, resulting in the cleavage of the ester bond. The enzyme is highly specific for its substrate and plays a crucial role in various biochemical pathways, including the degradation of gamma-hexachlorocyclohexane and 1,4-dichlorobenzene .

As of late 2007, ten structures have been solved for this class of enzymes, with Protein Data Bank (PDB) accession codes such as 1DIN, 1GGV, 1ZI6, 1ZI8, 1ZI9, 1ZIC, 1ZIX, 1ZIY, 1ZJ4, and 1ZJ5 . These structural studies have provided significant insights into the enzyme’s active site and its mechanism of action.

The gene encoding for CMBL is located on chromosome 5 in humans and is highly expressed in the liver cytosol . The enzyme is a cysteine hydrolase and is involved in the bioactivation of various prodrugs. For instance, it converts the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmesartan, an angiotensin receptor blocker, in the liver and intestine . Additionally, CMBL may also activate beta-lactam antibiotics such as faropenem medoxomil and lenampicillin .

CMBL’s ability to activate prodrugs makes it a significant enzyme in pharmacology. Its role in converting olmesartan medoxomil to olmesartan is particularly important for the treatment of hypertension. Moreover, the enzyme’s involvement in the degradation of environmental pollutants like gamma-hexachlorocyclohexane and 1,4-dichlorobenzene highlights its ecological importance .

Research on CMBL continues to explore its potential applications in medicine and environmental science. The enzyme’s specificity and efficiency in catalyzing hydrolysis reactions make it a promising candidate for biotechnological applications, including the development of new therapeutic agents and bioremediation strategies.