3EUT

X-ray crystal structure of a type III pentaketide synthase from Neurospora crassa

Summary for 3EUT

• Entry DOI: 10.2210/pdb3eut/pdb
• Related: 3EUQ
• Descriptor: Putative uncharacterized protein, icosanoic acid (3 entities in total)
• Functional Keywords: oras, acyltransferase, transferase
• Biological source: Neurospora crassa
• Total number of polymer chains: 4
• Total formula weight: 163823.70

Authors

Zhang, H.,Brunzelle, J.S.,Nair, S.K. (deposition date: 2008-10-10, release date: 2008-11-11, Last modification date: 2024-11-20)

Primary citation

Rubin-Pitel, S.B.,Zhang, H.,Vu, T.,Brunzelle, J.S.,Zhao, H.,Nair, S.K.
Distinct Structural Elements Dictate the Specificity of the Type III Pentaketide Synthase from Neurospora crassa.
Chem.Biol., 15:1079-1090, 2008

PubMed Abstract: The fungal type III polyketide synthase 2'-oxoalkylresorcylic acid synthase (ORAS) primes with a range of acyl-Coenzyme A thioesters (C4-C20) and extends using malonyl-Coenzyme A to produce pyrones, resorcinols, and resorcylic acids. To gain insight into this unusual substrate specificity and product profile, we have determined the crystal structures of ORAS to 1.75 A resolution, the Phe-252-->Gly site-directed mutant to 2.1 A resolution, and a binary complex of ORAS with eicosanoic acid to 2.0 A resolution. The structures reveal a distinct rearrangement of structural elements near the active site that allows accommodation of long-chain fatty acid esters and a reorientation of the gating mechanism that controls cyclization and polyketide chain length. The roles of these structural elements are further elucidated by characterization of various structure-based site-directed variants. These studies establish an unexpected plasticity to the PKS fold, unanticipated from structural studies of other members of this enzyme family.

PubMed: 18940668
DOI: 10.1016/j.chembiol.2008.08.011

Experimental method

X-RAY DIFFRACTION (2 Å)