4OPE

Streptomcyes albus JA3453 oxazolomycin ketosynthase domain OzmH KS7

Summary for 4OPE

• Entry DOI: 10.2210/pdb4ope/pdb
• Related: 4OPF 4OQJ 4QYR 4TKT 4WKY 4ZDN
• Descriptor: NRPS/PKS, NITRATE ION (3 entities in total)
• Functional Keywords: structural genomics, pks, ozmh, psi-biology, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro, ligase, transferase
• Biological source: Streptomyces albus
• Total number of polymer chains: 4
• Total formula weight: 250276.39

Authors

Osipiuk, J.,Mack, J.,Endres, M.,Babnigg, G.,Bingman, C.A.,Yennamalli, R.,Lohman, J.R.,Ma, M.,Shen, B.,Phillips Jr., G.N.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Enzyme Discovery for Natural Product Biosynthesis (NatPro) (deposition date: 2014-02-05, release date: 2014-02-19, Last modification date: 2018-01-24)

Primary citation

Lohman, J.R.,Ma, M.,Osipiuk, J.,Nocek, B.,Kim, Y.,Chang, C.,Cuff, M.,Mack, J.,Bigelow, L.,Li, H.,Endres, M.,Babnigg, G.,Joachimiak, A.,Phillips, G.N.,Shen, B.
Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases.
Proc.Natl.Acad.Sci.USA, 112:12693-12698, 2015

PubMed Abstract: Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS paradigm. They lack the integrated AT domains within their modules and instead use a discrete AT that acts in trans, whereas a type I PKS module minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains. Structures of canonical type I PKS KS-AT didomains reveal structured linkers that connect the two domains. AT-less type I PKS KSs have remnants of these linkers, which have been hypothesized to be AT docking domains. Natural products produced by AT-less type I PKSs are very complex because of an increased representation of unique modifying domains. AT-less type I PKS KSs possess substrate specificity and fall into phylogenetic clades that correlate with their substrates, whereas canonical type I PKS KSs are monophyletic. We have solved crystal structures of seven AT-less type I PKS KS domains that represent various sequence clusters, revealing insight into the large structural and subtle amino acid residue differences that lead to unique active site topologies and substrate specificities. One set of structures represents a larger group of KS domains from both canonical and AT-less type I PKSs that accept amino acid-containing substrates. One structure has a partial AT-domain, revealing the structural consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These structures highlight the structural diversity within the AT-less type I PKS KS family, and most important, provide a unique opportunity to study the molecular evolution of substrate specificity within the type I PKSs.

PubMed: 26420866
DOI: 10.1073/pnas.1515460112

Experimental method

X-RAY DIFFRACTION (2.58 Å)