1xkt: Difference between revisions
New page: left|200px<br /> <applet load="1xkt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xkt, resolution 2.60Å" /> '''Human fatty acid sy... |
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[[Image:1xkt.gif|left|200px]]<br /> | [[Image:1xkt.gif|left|200px]]<br /><applet load="1xkt" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1xkt, resolution 2.60Å" /> | caption="1xkt, resolution 2.60Å" /> | ||
'''Human fatty acid synthase: Structure and substrate selectivity of the thioesterase domain'''<br /> | '''Human fatty acid synthase: Structure and substrate selectivity of the thioesterase domain'''<br /> | ||
==Overview== | ==Overview== | ||
Human fatty acid synthase is a large homodimeric multifunctional enzyme | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1XKT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1XKT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XKT OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chakravarty, B.]] | [[Category: Chakravarty, B.]] | ||
[[Category: Chirala, S | [[Category: Chirala, S S.]] | ||
[[Category: Gu, Z.]] | [[Category: Gu, Z.]] | ||
[[Category: Quiocho, F | [[Category: Quiocho, F A.]] | ||
[[Category: Wakil, S | [[Category: Wakil, S J.]] | ||
[[Category: drug target]] | [[Category: drug target]] | ||
[[Category: human fatty acid synthase]] | [[Category: human fatty acid synthase]] | ||
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[[Category: thioesterase]] | [[Category: thioesterase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:55:48 2008'' | ||
Revision as of 16:55, 21 February 2008
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Human fatty acid synthase: Structure and substrate selectivity of the thioesterase domain
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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