4IMP

The missing linker: a dimerization motif located within polyketide synthase modules

Summary for 4IMP

• Entry DOI: 10.2210/pdb4imp/pdb
• Descriptor: Polyketide synthase extender modules 3-4, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: dimerization element, transferase
• Biological source: Saccharopolyspora spinosa
• Total number of polymer chains: 4
• Total formula weight: 249379.98

Authors

Zheng, J.,Keatinge-Clay, A.T. (deposition date: 2013-01-03, release date: 2013-03-27, Last modification date: 2023-09-20)

Primary citation

Zheng, J.,Fage, C.D.,Demeler, B.,Hoffman, D.W.,Keatinge-Clay, A.T.
The missing linker: a dimerization motif located within polyketide synthase modules.
Acs Chem.Biol., 8:1263-1270, 2013

PubMed Abstract: The dimerization of multimodular polyketide synthases is essential for their function. Motifs that supplement the contacts made by dimeric polyketide synthase enzymes have previously been characterized outside the boundaries of modules, at the N- and C-terminal ends of polyketide synthase subunits. Here we describe a heretofore uncharacterized dimerization motif located within modules. The dimeric state of this dimerization element was elucidated through the 2.6 Å resolution crystal structure of a fragment containing a dimerization element and a ketoreductase. The solution structure of a standalone dimerization element was revealed by nuclear magnetic resonance spectroscopy to be consistent with that of the crystal structure, and its dimerization constant was measured through analytical ultracentrifugation to be ∼20 μM. The dimer buries ∼990 Å(2) at its interface, and its C-terminal helices rigidly connect to ketoreductase domains to constrain their locations within a module. These structural restraints permitted the construction of a common type of polyketide synthase module.

PubMed: 23489133
DOI: 10.1021/cb400047s

Experimental method

X-RAY DIFFRACTION (2.57 Å)