PDBsum entry 4zdn

Transferase

PDB id: 4zdn

Contents

Protein chain

589 a.a.

Ligands

EPE

Metals

_CL

Waters ×126

PDB id:

4zdn

Name:

Transferase

Title:

Streptomyces platensis isomigrastatin ketosynthase domain mgsf ks4

Structure:

At-less polyketide synthase. Chain: a. Fragment: residues 550-1188. Engineered: yes

Source:

Streptomyces platensis subsp. Rosaceus. Organism_taxid: 684832. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.51Å R-factor: 0.189 R-free: 0.226

Authors:

C.Chang,H.Li,M.Endres,C.A.Bingman,R.Yennamalli,J.R.Lohman,M.Ma, B.Shen,G.N.Phillips Jr.,A.Joachimiak,Midwest Center For Structural Genomics (Mcsg),Enzyme Discovery For Natural Product Biosynthesis (Natpro)

Key ref:

J.R.Lohman et al. (2015). Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases. Proc Natl Acad Sci U S A, 112, 12693-12698. PubMed id: 26420866 DOI: 10.1073/pnas.1515460112

Date:

17-Apr-15 Release date: 13-May-15

Supersedes:

4tl2

Protein chain

D0U2E4  (D0U2E4_STRPT) -  AT-less polyketide synthase from Streptomyces platensis subsp. rosaceus

Seq: 8026 a.a.

Struc: 589 a.a.

DOI no: 10.1073/pnas.1515460112

Proc Natl Acad Sci U S A 112:12693-12698 (2015)

PubMed id: 26420866

Structural and evolutionary relationships of "AT-less" type I polyketide synthase ketosynthases.

J.R.Lohman, M.Ma, J.Osipiuk, B.Nocek, Y.Kim, C.Chang, M.Cuff, J.Mack, L.Bigelow, H.Li, M.Endres, G.Babnigg, A.Joachimiak, G.N.Phillips, B.Shen.

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.