PDBsum entry 1af8

Antibiotic biosynthesis

PDB id: 1af8

Contents

Protein chain

86 a.a. *

* Residue conservation analysis

PDB id:

1af8

Name:

Antibiotic biosynthesis

Title:

Actinorhodin polyketide synthase acyl carrier protein from streptomyces coelicolor a3(2), nmr, 24 structures

Structure:

Actinorhodin polyketide synthase acyl carrier protein. Chain: a. Synonym: act acp, acti orf3. Engineered: yes

Source:

Streptomyces coelicolor. Organism_taxid: 100226. Strain: a3(2). Gene: actinorhodin acyl carrier protein. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

24 models

Authors:

M.P.Crump,J.Crosby,C.E.Dempsey,J.A.Parkinson,M.Murray,D.A.Hopwood, T.J.Simpson

Key ref:

M.P.Crump et al. (1997). Solution structure of the actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2). Biochemistry, 36, 6000-6008. PubMed id: 9166770 DOI: 10.1021/bi970006+

Date:

23-Mar-97 Release date: 26-Sep-97

Protein chain

Q02054  (ACPX_STRCO) -  Actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)

Seq: 86 a.a.

Struc: 86 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi970006+

Biochemistry 36:6000-6008 (1997)

PubMed id: 9166770

Solution structure of the actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2).

M.P.Crump, J.Crosby, C.E.Dempsey, J.A.Parkinson, M.Murray, D.A.Hopwood, T.J.Simpson.

ABSTRACT

The solution structure of the actinorhodin acyl carrier protein (act apo-ACP) from the polyketide synthase (PKS) of Streptomyces coelicolor A3(2) has been determined using 1H NMR spectroscopy, representing the first polyketide synthase component for which detailed structural information has been obtained. Twenty-four structures were generated by simulated annealing, employing 699 distance restraints and 94 dihedral angle restraints. The structure is composed, principally, of three major helices (1, 2, and 4), a shorter helix (3) and a large loop region separating helices 1 and 2. The structure is well-defined, except for a portion of the loop region (residues 18-29), the N-terminus (1-4), and a short stretch (57-61) in the loop connecting helices 2 and 3. The RMS distribution of the 24 structures about the average structure is 1.47 A for backbone atoms, 1.84 A for all heavy atoms (residues 5-86), and 1.01 A for backbone atoms over the helical regions (5-18, 41-86). The tertiary fold of act apo-ACP shows a strong structural homology with Escherichia coli fatty acid synthase (FAS) ACP, though some structural differences exist. First, there is no evidence that act apo-ACP is conformationally averaged between two or more states as observed in E. coli FAS ACP. Second, act apo-ACP shows a disordered N-terminus (residues 1-4) and a longer flexible loop (19-41 with 19-29 disordered) as opposed to E. coli FAS ACP where the N-terminal helix starts at residue 3 and the loop region is three amino acids shorter (16-35). Most importantly, however, although the act apo-ACP structure contains a hydrophobic core, there are in addition a number of buried hydrophilic groups, principally Arg72 and Asn79, both of which are 100% conserved in the PKS ACPs and not the FAS ACPs and may therefore play a role in stabilizing the growing polyketide chain. The structure-function relationship of act ACP is discussed in the light of these structural data and recent genetic advances in the field.