CMBL Antibodies

Background

CMBL is a hydrolase present in various organisms, mainly distributed in metabolically active tissues such as the liver and kidneys. The protein encoded by this gene can specifically catalyze the hydrolysis reaction of carboxymethyl enol compounds, and participate in the detoxification metabolic pathways and energy metabolism regulation processes of exogenous toxins in vivo. Studies have shown that CMBL plays a key role in individual differences in drug metabolism, and its activity level can affect the efficacy and safety of certain clinical drugs. This gene was first identified by a Japanese research team in 2004, and its three-dimensional protein structure revealed the substrate-specific mechanism through crystallographic analysis in 2010. As an important model protein in metabolic research, CMBL provides a key molecular basis for understanding the evolution of enzyme kinetics, heterologous substance metabolism and individualized medication.

Structure Function Application Advantage Our Products

Structure of CMBL

CMBL is a hydrolase with a molecular weight of approximately 28.5 kDa. Its precise molecular weight may fluctuate slightly due to minor differences in amino acid sequences among species.

Species	Human	Mouse	Rat	Macaque	Domestic dog
Molecular Weight (kDa)	28.5	28.3	28.4	28.6	28.5
Primary Structural Differences	Standard reference sequence	Two conservative sites are replaced	One amino acid is missing at the C-terminal	High homology with humans	The active site is completely conserved

This protein is composed of 253 amino acids, and its spatial structure presents a typical α/β hydrolase folding conformation. The active center of CMBL contains a catalytic triad (Ser144-His268-Asp240) composed of serine, histidine and aspartic acid, and this conserved structure is the core basis of its hydrolase function. Its tertiary structure forms a deep hydrophobic underwater binding pocket that can specifically recognize carboxymethyl enol compounds. The charge distribution characteristics on the surface of proteins determine their binding affinity and catalytic efficiency with specific drug substrates.

CMBL Enzyme Evolution and Differentiation. Fig. 1 Research on the Evolution and Functional Differentiation of CMBL Homologous Enzymes Based on Structural Conservation.¹

Key structural properties of CMBL:

Classic α/β hydrolase folded conformation
Composed of serine, histidine and aspartic acid catalytic triplets
Deep hydrophobic underwater binding pockets are used to identify specific compounds
Keep the charge distribution of surface determines the substrate specificity of binding and catalytic efficiency

Functions of CMBL

The main function of CMBL protein is to participate in the metabolic detoxification of exogenous substances (such as drugs). In addition, it also involves some important physiological and pathological processes within the body, including differences in drug efficacy and cellular stress responses.

Function	Description
Drug metabolism	Catalyzing the hydrolysis and activation of various carboxymethyl enol prodrugs is a key initiating step in the in vivo metabolism of many clinical drugs, such as ticagrelor.
Detoxification effect	Hydrolyze specific exogenous toxins ingested into the body and convert them into water-soluble substances that are easy to be excreted from the body, thereby achieving a biological detoxification effect.
Individualized medication	Its gene polymorphism and expression level are important factors causing differences in drug metabolism rate and efficacy among individuals, directly affecting clinical medication strategies.
Cell protection	By eliminating certain potential electrophilic metabolites, it reduces the damage these substances cause to cellular proteins and DNA, providing a certain degree of cellular protection.
Biomarker	Its expression activity can serve as a potential biomarker for assessing an individual's ability to metabolize specific drugs, and is used to predict drug responses and toxicity risks.

The enzymatic kinetics of CMBL follows the typical Michaelis-Menten kinetics. Its hydrolysis efficiency depends on the substrate concentration and the genetic polymorphism of the enzyme itself, which is quite different from hemoglobin with a synergistic effect, indicating its role as a regulated key enzyme in metabolism.

Applications of CMBL and CMBL Antibody in Literature

1. Niu, Nifang, et al. "Genetic association with overall survival of taxane-treated lung cancer patients-a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study." BMC cancer 12.1 (2012): 422. https://doi.org/10.1186/1471-2407-12-422

Through GWAS and functional studies, it was found that the SNP rs2662411 near the CMBL gene was associated with the overall survival of lung cancer patients after paclitaxel treatment. This SNP may affect the expression of CMBL by regulating hsa-miR-584, thereby regulating drug sensitivity.

2. Bergmann, Lutgardis, et al. "New dienelactone hydrolase from microalgae bacterial community-Antibiofilm activity against fish pathogens and potential applications for aquaculture." Scientific Reports 14.1 (2024): 377. https://doi.org/10.1038/s41598-023-50734-9

Based on the aquatic microbiome mining, it was found that dienolactonase (CMBL) Dlh3 could effectively inhibit the biofilm formation of S. ictalinus by 54.5% and was harmless to fish cells, indicating a good application in aquaculture.

3. Schwarz, Marcos Gustavo Araujo, et al. "Revisiting jatropha curcas monomeric esterase: A dienelactone hydrolase compatible with the electrostatic catapult model." Biomolecules 11.10 (2021): 1486. https://doi.org/10.3390/biom11101486

The article indicates that the esterase from the seeds of the Jatropha rubrica has been identified as belonging to the dienolactone hydrolase family (CMBL), with cysteine as the nucleophilic catalyst. The optimal pH for hydrolysis is 9.0, and it has low activity in organic solvents but can recover in the aqueous phase. It is suitable for the hydrolysis of short-chain esters and the synthesis of drug intermediates under alkaline conditions.

4. Xu, Hongyan, et al. "Genome-wide identification of molecular pathways and biomarkers in response to arsenic exposure in zebrafish liver." PloS one 8.7 (2013): e68737. https://doi.org/10.1371/journal.pone.0068737

This study analyzed the liver transcriptome response to arsenic exposure through sequencing technology and found that genes such as CMBL (a homolog of carboxymethyl butylated lactone) were significantly upregulated. The cross-species applicability of these genes as potential biomarkers of arsenic exposure was confirmed by multi-species validation, revealing the molecular mechanisms of arsenic toxicity involving oxidative stress and metabolic disorders.

5. Ishizuka, Tomoko, et al. "Human carboxymethylenebutenolidase as a bioactivating hydrolase of olmesartan medoxomil in liver and intestine." Journal of Biological Chemistry 285.16 (2010): 11892-11902. https://doi.org/10.1074/jbc.M109.072629

This study has for the first time confirmed that human CMBL (carboxymethyl butylated lactase homolog) is a key activating enzyme for precursor drugs such as olmesartan esters. It can specifically hydrolyze their ester bonds in the liver and intestines to generate active metabolites and relies on the Cys132 residue to exert catalytic functions.

Creative Biolabs: CMBL Antibodies for Research

Creative Biolabs specializes in the production of high-quality CMBL antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom CMBL Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CMBL antibodies, custom preparations, or technical support, contact us at email.

Reference

Bergmann, Lutgardis, et al. "New dienelactone hydrolase from microalgae bacterial community-Antibiofilm activity against fish pathogens and potential applications for aquaculture." Scientific Reports 14.1 (2024): 377. https://doi.org/10.1038/s41598-023-50734-9