2hfk

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{{STRUCTURE_2hfk| PDB=2hfk | SCENE= }}
{{STRUCTURE_2hfk| PDB=2hfk | SCENE= }}
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'''Pikromycin thioesterase in complex with product 10-deoxymethynolide'''
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===Pikromycin thioesterase in complex with product 10-deoxymethynolide===
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==Overview==
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Polyketides are a class of biologically active microbial and plant-derived metabolites that possess a high degree of structural and functional diversity and include many human therapeutics, among them anti-infective and anti-cancer drugs, growth promoters and anti-parasitic agents. The macrolide antibiotics, characterized by a glycoside-linked macrolactone, constitute an important class of polyketides, including erythromycin and the natural ketolide anti-infective agent pikromycin. Here we describe new mechanistic details of macrolactone ring formation catalyzed by the pikromycin polyketide synthase thioesterase domain from Streptomyces venezuelae. A pentaketide phosphonate mimic of the final pikromycin linear chain-elongation intermediate was synthesized and shown to be an active site affinity label. The crystal structures of the affinity-labeled enzyme and of a 12-membered-ring macrolactone product complex suggest a mechanism for cyclization in which a hydrophilic barrier in the enzyme and structural restraints of the substrate induce a curled conformation to direct macrolactone ring formation.
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(as it appears on PubMed at http://www.pubmed.gov), where 16969372 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16969372}}
==About this Structure==
==About this Structure==
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[[Category: Alpha/beta hydrolase]]
[[Category: Alpha/beta hydrolase]]
[[Category: Thioesterase]]
[[Category: Thioesterase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:13:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:37:36 2008''

Revision as of 14:37, 28 July 2008

Image:2hfk.png

Template:STRUCTURE 2hfk

Pikromycin thioesterase in complex with product 10-deoxymethynolide

Template:ABSTRACT PUBMED 16969372

About this Structure

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

Reference

Structural basis for macrolactonization by the pikromycin thioesterase., Akey DL, Kittendorf JD, Giraldes JW, Fecik RA, Sherman DH, Smith JL, Nat Chem Biol. 2006 Oct;2(10):537-42. Epub 2006 Sep 10. PMID:16969372

Page seeded by OCA on Mon Jul 28 17:37:36 2008

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