Document Detail


Structural and functional analysis of tetracenomycin F2 cyclase from Streptomyces glaucescens. A type II polyketide cyclase.
MedLine Citation:
PMID:  15231835     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tetracenomycin F2 cyclase (tcmI gene product), catalyzes an aromatic rearrangement in the biosynthetic pathway for tetracenomycin C in Streptomyces glaucescens. The x-ray structure of this small enzyme has been determined to 1.9-A resolution together with an analysis of site-directed mutants of potential catalytic residues. The protein exhibits a dimeric betaalphabeta ferredoxin-like fold that utilizes strand swapping between subunits in its assembly. The fold is dominated by four strands of antiparallel sheet and a layer of alpha-helices, which creates a cavity that is proposed to be the active site. This type of secondary structural arrangement has been previously observed in polyketide monooxygenases and suggests an evolutionary relationship between enzymes that catalyze adjacent steps in these biosynthetic pathways. Mutational analysis of all of the obvious catalytic bases within the active site suggests that the enzyme functions to steer the chemical outcome of the cyclization rather than providing a specific catalytic group. Together, the structure and functional analysis provide insight into the structural framework necessary to perform the complex rearrangements catalyzed by this class of polyketide cyclases.
Authors:
Thomas B Thompson; Kinya Katayama; Kenji Watanabe; C Richard Hutchinson; Ivan Rayment
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2004-06-30
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-30     Completed Date:  2004-12-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37956-63     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/1TUW
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MeSH Terms
Descriptor/Qualifier:
Aldehyde-Lyases / chemistry*,  metabolism*
Bacterial Proteins / chemistry*,  metabolism*
Base Sequence
Catalysis
Crystallography, X-Ray
DNA Primers
Kinetics
Models, Molecular
Protein Conformation
Streptomyces / enzymology*
Grant Support
ID/Acronym/Agency:
AR35186/AR/NIAMS NIH HHS; GM08293/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/DNA Primers; EC 4.1.2.-/Aldehyde-Lyases; EC 4.1.2.-/tetracenomycin F2 cyclase, Streptomyces

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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