2h7y: Difference between revisions

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[[Image:2h7y.gif|left|200px]]
{{Seed}}
[[Image:2h7y.png|left|200px]]


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{{STRUCTURE_2h7y|  PDB=2h7y  |  SCENE=  }}  
{{STRUCTURE_2h7y|  PDB=2h7y  |  SCENE=  }}  


'''Pikromycin Thioesterase with covalent affinity label'''
===Pikromycin Thioesterase with covalent affinity label===




==Overview==
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Polyketides are a diverse class of natural products having important clinical properties, including antibiotic, immunosuppressive and anticancer activities. They are biosynthesized by polyketide synthases (PKSs), which are modular, multienzyme complexes that sequentially condense simple carboxylic acid derivatives. The final reaction in many PKSs involves thioesterase-catalyzed cyclization of linear chain elongation intermediates. As the substrate in PKSs is presented by a tethered acyl carrier protein, introduction of substrate by diffusion is problematic, and no substrate-bound type I PKS domain structure has been reported so far. We describe the chemical synthesis of polyketide-based affinity labels that covalently modify the active site serine of excised pikromycin thioesterase from Streptomyces venezuelae. Crystal structures reported here of the affinity label-pikromycin thioesterase adducts provide important mechanistic insights. These results suggest that affinity labels can be valuable tools for understanding the mechanisms of individual steps within multifunctional PKSs and for directing rational engineering of PKS domains for combinatorial biosynthesis.
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{{ABSTRACT_PUBMED_16969373}}


==About this Structure==
==About this Structure==
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[[Category: Alpha/beta hydrolase]]
[[Category: Alpha/beta hydrolase]]
[[Category: Thioesterase]]
[[Category: Thioesterase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:58:40 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:24:04 2008''

Revision as of 23:24, 28 July 2008

File:2h7y.png

Template:STRUCTURE 2h7y

Pikromycin Thioesterase with covalent affinity label

Template:ABSTRACT PUBMED 16969373

About this Structure

2H7Y is a Single protein structure of sequence from Streptomyces venezuelae. Full crystallographic information is available from OCA.

Reference

Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels., Giraldes JW, Akey DL, Kittendorf JD, Sherman DH, Smith JL, Fecik RA, Nat Chem Biol. 2006 Oct;2(10):531-6. Epub 2006 Sep 10. PMID:16969373

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