8jaw

From Proteopedia

Human MCC in MCCD state

Structural highlights

8jaw is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.51Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MCCB_HUMAN 3-methylcrotonyl-CoA carboxylase deficiency. The disease is caused by variants affecting the gene represented in this entry.

Function

MCCB_HUMAN Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.^[1]

Publication Abstract from PubMed

The enzymes 3-methylcrotonyl-coenzyme A (CoA) carboxylase (MCC), pyruvate carboxylase and propionyl-CoA carboxylase belong to the biotin-dependent carboxylase family located in mitochondria. They participate in various metabolic pathways in human such as amino acid metabolism and tricarboxylic acid cycle. Many human diseases are caused by mutations in those enzymes but their structures have not been fully resolved so far. Here we report an optimized purification strategy to obtain high-resolution structures of intact human endogenous MCC, propionyl-CoA carboxylase and pyruvate carboxylase in different conformational states. We also determine the structures of MCC bound to different substrates. Analysis of MCC structures in different states reveals the mechanism of the substrate-induced, multi-element synergistic activation of MCC. These results provide important insights into the catalytic mechanism of the biotin-dependent carboxylase family and are of great value for the development of new drugs for the treatment of related diseases.

Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase.,Su J, Tian X, Cheng H, Liu D, Wang Z, Sun S, Wang HW, Sui SF Nat Struct Mol Biol. 2024 Sep 2. doi: 10.1038/s41594-024-01379-3. PMID:39223421^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chu CH, Cheng D. Expression, purification, characterization of human 3-methylcrotonyl-CoA carboxylase (MCCC). Protein Expr Purif. 2007 Jun;53(2):421-7. PMID:17360195 doi:10.1016/j.pep.2007.01.012
↑ Su J, Tian X, Cheng H, Liu D, Wang Z, Sun S, Wang HW, Sui SF. Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase. Nat Struct Mol Biol. 2024 Sep 2. PMID:39223421 doi:10.1038/s41594-024-01379-3