PDBsum entry 2d51

Transferase

PDB id: 2d51

Contents

Protein chains

405 a.a. *

Waters ×592

* Residue conservation analysis

PDB id:

2d51

Name:

Transferase

Title:

Pentaketide chromone synthase (m207g mutant)

Structure:

Pentaketide chromone synthase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Aloe arborescens. Organism_taxid: 45385. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.192 R-free: 0.208

Authors:

T.Kohno,H.Morita

Key ref:

H.Morita et al. (2007). Structural insight into chain-length control and product specificity of pentaketide chromone synthase from Aloe arborescens. Chem Biol, 14, 359-369. PubMed id: 17462571 DOI: 10.1016/j.chembiol.2007.02.003

Date:

27-Oct-05 Release date: 14-Nov-06

Protein chains

Q58VP7  (PCS_ALOAR) -  5,7-dihydroxy-2-methylchromone synthase from Aloe arborescens

Seq: 403 a.a.

Struc: 405 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.3.1.216 - 5,7-dihydroxy-2-methylchromone synthase.
• Reaction: 5 malonyl-CoA + 4 H⁺ = 5,7-dihydroxy-2-methyl-4H-chromen-4-one + 5 CO2 + 5 CoA + H2O

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.chembiol.2007.02.003

Chem Biol 14:359-369 (2007)

PubMed id: 17462571

Structural insight into chain-length control and product specificity of pentaketide chromone synthase from Aloe arborescens.

H.Morita, S.Kondo, S.Oguro, H.Noguchi, S.Sugio, I.Abe, T.Kohno.

ABSTRACT

The crystal structures of a wild-type and a mutant PCS, a novel plant type III polyketide synthase from a medicinal plant, Aloe arborescens, were solved at 1.6 A resolution. The crystal structures revealed that the pentaketide-producing wild-type and the octaketide-producing M207G mutant shared almost the same overall folding, and that the large-to-small substitution dramatically increases the volume of the polyketide-elongation tunnel by opening a gate to two hidden pockets behind the active site of the enzyme. The chemically inert active site residue 207 thus controls the number of condensations of malonyl-CoA, solely depending on the steric bulk of the side chain. These findings not only provided insight into the polyketide formation reaction, but they also suggested strategies for the engineered biosynthesis of polyketides.

Selected figure(s)

Figure 3.
Figure 3. Overall Structure of PCS Complexed with CoA-SH
(A) Ribbon representation of the PCS homodimer. The monomers are colored green and silver, and the CoA-SH molecules are shown as blue stick models. The catalytic Cys174 and Met147, which form a partial wall of the active-site cavity of another monomer, are highlighted as yellow CPK and stick models, respectively.
(B) Comparison of PCS (green), M. sativa CHS (blue), and G. hybrida 2PS (purple). The catalytic Cys174 and the bound CoA-SH in PCS are also shown as yellow and red CPK molecules, respectively.
(C) CoA-SH binding to the PCS structure. The CoA-SH (green) and the SIGMA-weighted |2F[o] − F[c]| electron density (0.8σ, red cage) for CoA-SH are shown. The water molecules (light-blue spheres) and hydrogen bonds (dotted lines) are also indicated.

Figure 6.
Figure 6. Schematic Representation of the Active-Site Architecture of Wild-Type PCS, the M207G Mutant, and M. sativa CHS
(A–C) The M207G substitution opens a gate to the buried pocket A that extends into the “floor” of the active-site cavity, resulting in a 4:1 mixture of SEK4b:SEK4 instead of 5,7-dihydroxy- 2-methylchormone. PCS locks the methyl end of its linear pentaketide intermediate between Met207 and Val351, as in the case in which M. sativa CHS locks the aromatic ring derived from 4-coumaroyl-CoA with the coumaroyl-binding pocket.

The above figures are reprinted by permission from Cell Press: Chem Biol (2007, 14, 359-369) copyright 2007.

Figures were selected by an automated process.