1TUW

Structural and Functional Analysis of Tetracenomycin F2 Cyclase from Streptomyces glaucescens: A Type-II Polyketide Cyclase

Summary for 1TUW

• Entry DOI: 10.2210/pdb1tuw/pdb
• Descriptor: Tetracenomycin polyketide synthesis protein tcmI, SULFATE ION (3 entities in total)
• Functional Keywords: dimeric ??? ferredoxin-like fold tetracenomycin c biosynthesis, unknown function
• Biological source: Streptomyces glaucescens
• Total number of polymer chains: 1
• Total formula weight: 12973.51

Authors

Thompson, T.B.,Katayama, K.,Watanabe, K.,Hutchinson, C.R.,Rayment, I. (deposition date: 2004-06-25, release date: 2004-08-03, Last modification date: 2024-02-14)

Primary citation

Thompson, T.B.,Katayama, K.,Watanabe, K.,Hutchinson, C.R.,Rayment, I.
Structural and functional analysis of tetracenomycin F2 cyclase from Streptomyces glaucescens. A type II polyketide cyclase.
J.Biol.Chem., 279:37956-37963, 2004

PubMed Abstract: 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.

PubMed: 15231835
DOI: 10.1074/jbc.M406144200

Experimental method

X-RAY DIFFRACTION (1.9 Å)