Structural highlights
Disease
ACACA_HUMAN Defects in ACACA are a cause of acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:613933; also known as ACAC deficiency or ACC deficiency. An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.[1]
Function
ACACA_HUMAN Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.[2]
Publication Abstract from PubMed
Human acetyl-coenzyme A (CoA) carboxylases (ACCs) catalyze the carboxylation of acetyl-CoA, which is the rate-limiting step in fatty acid synthesis. The molecular mechanism underlying the dynamic organization of ACCs is largely unknown. Here, we determined the cryo-electron microscopy (EM) structure of human ACC1 in its inactive state, which forms a unique filament structure and is in complex with acetyl-CoA. We also determined the cryo-EM structure of human ACC1 activated by dephosphorylation and citrate treatment, at a resolution of 2.55 A. Notably, the covalently linked biotin binds to a site that is distant from the acetyl-CoA binding site when acetyl-CoA is absent, suggesting a potential coordination between biotin binding and acetyl-CoA binding. These findings provide insights into the structural dynamics and regulatory mechanisms of human ACCs.
Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase.,Zhou F, Zhang Y, Zhu Y, Zhou Q, Shi Y, Hu Q Sci Adv. 2024 Oct 11;10(41):eado4880. doi: 10.1126/sciadv.ado4880. Epub 2024 Oct , 9. PMID:39383219[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Blom W, de Muinck Keizer SM, Scholte HR. Acetyl-CoA carboxylase deficiency: an inborn error of de novo fatty acid synthesis. N Engl J Med. 1981 Aug 20;305(8):465-6. PMID:6114432 doi:http://dx.doi.org/10.1056/NEJM198108203050820
- ↑ Colbert CL, Kim CW, Moon YA, Henry L, Palnitkar M, McKean WB, Fitzgerald K, Deisenhofer J, Horton JD, Kwon HJ. Crystal structure of Spot 14, a modulator of fatty acid synthesis. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18820-5. Epub 2010 Oct 15. PMID:20952656 doi:10.1073/pnas.1012736107
- ↑ Zhou F, Zhang Y, Zhu Y, Zhou Q, Shi Y, Hu Q. Filament structures unveil the dynamic organization of human acetyl-CoA carboxylase. Sci Adv. 2024 Oct 11;10(41):eado4880. PMID:39383219 doi:10.1126/sciadv.ado4880
