1xkt
Human fatty acid synthase: Structure and substrate selectivity of the thioesterase domain
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OverviewOverview
Human fatty acid synthase is a large homodimeric multifunctional enzyme, that synthesizes palmitic acid. The unique carboxyl terminal thioesterase, domain of fatty acid synthase hydrolyzes the growing fatty acid chain and, plays a critical role in regulating the chain length of fatty acid, released. Also, the up-regulation of human fatty acid synthase in a, variety of cancer makes the thioesterase a candidate target for, therapeutic treatment. The 2.6-A resolution structure of human fatty acid, synthase thioesterase domain reported here is comprised of two dissimilar, subdomains, A and B. The smaller subdomain B is composed entirely of, alpha-helices arranged in an atypical fold, whereas the A subdomain is a, variation of the alpha/beta hydrolase fold. The structure revealed the, presence of a hydrophobic groove with a distal pocket at the interface of, the two subdomains, which constitutes the candidate substrate binding, site. The length and largely hydrophobic nature of the groove and pocket, are consistent with the high selectivity of the thioesterase for palmitoyl, acyl substrate. The structure also set the identity of the Asp residue of, the catalytic triad of Ser, His, and Asp located in subdomain A at the, proximal end of the groove.
DiseaseDisease
Known diseases associated with this structure: Autoimmune lymphoproliferative syndrome OMIM:[134637], Autoimmune lymphoproliferative syndrome, type IA OMIM:[134637], Squamous cell carcinoma, burn scar-related, somatic OMIM:[134637]
About this StructureAbout this Structure
1XKT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain., Chakravarty B, Gu Z, Chirala SS, Wakil SJ, Quiocho FA, Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15567-72. Epub 2004 Oct 26. PMID:15507492
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