Dataset Information

Crystallization and structure analysis of the core motif of the Pks13 acyltransferase domain from Mycobacterium tuberculosis.

ABSTRACT: Type I polyketide synthase 13 (Pks13) is involved in the final step of the biosynthesis of mycolic acid in Mycobacterium tuberculosis. Recent articles have reported that Pks13 is an essential enzyme in the mycolic acid biosynthesis pathway, and it has been deeply studied as a drug target in Tuberculosis. We report a high-resolution structure of the acyltransferase (AT) domain of Pks13 at 2.59 Å resolution. Structural comparison with the full-length AT domain (PDB code, 3TZW, and 3TZZ) reveals a different orientation of the C-terminal helix and rearrangement of some conserved residues.

SUBMITTER: Yu M

PROVIDER: S-EPMC5944431 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Crystallization and structure analysis of the core motif of the Pks13 acyltransferase domain from <i>Mycobacterium tuberculosis</i>.

Yu Mingjing M Dou Chao C Gu Yijun Y Cheng Wei W

PeerJ 20180507

Type I polyketide synthase 13 (Pks13) is involved in the final step of the biosynthesis of mycolic acid in <i>Mycobacterium tuberculosis</i>. Recent articles have reported that Pks13 is an essential enzyme in the mycolic acid biosynthesis pathway, and it has been deeply studied as a drug target in Tuberculosis. We report a high-resolution structure of the acyltransferase (AT) domain of Pks13 at 2.59 Å resolution. Structural comparison with the full-length AT domain (PDB code, 3TZW, and 3TZZ) rev ...[more]

PMID: 29761048

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Project description:BackgroundType I polyketide synthases (PKSs) are multifunctional enzymes responsible for the biosynthesis of a group of diverse natural compounds with biotechnological and pharmaceutical interest called polyketides. The diversity of polyketides is impressive despite the limited set of catalytic domains used by PKSs for biosynthesis, leading to considerable interest in deciphering their structure-function relationships, which is challenging due to high intrinsic flexibility. Among nineteen polyketide synthases encoded by the genome of Mycobacterium tuberculosis, Pks13 is the condensase required for the final condensation step of two long acyl chains in the biosynthetic pathway of mycolic acids, essential components of the cell envelope of Corynebacterineae species. It has been validated as a promising druggable target and knowledge of its structure is essential to speed up drug discovery to fight against tuberculosis.ResultsWe report here a quasi-atomic model of Pks13 obtained using small-angle X-ray scattering of the entire protein and various molecular subspecies combined with known high-resolution structures of Pks13 domains or structural homologues. As a comparison, the low-resolution structures of two other mycobacterial polyketide synthases, Mas and PpsA from Mycobacterium bovis BCG, are also presented. This study highlights a monomeric and elongated state of the enzyme with the apo- and holo-forms being identical at the resolution probed. Catalytic domains are segregated into two parts, which correspond to the condensation reaction per se and to the release of the product, a pivot for the enzyme flexibility being at the interface. The two acyl carrier protein domains are found at opposite sides of the ketosynthase domain and display distinct characteristics in terms of flexibility.ConclusionsThe Pks13 model reported here provides the first structural information on the molecular mechanism of this complex enzyme and opens up new perspectives to develop inhibitors that target the interactions with its enzymatic partners or between catalytic domains within Pks13 itself.

Dataset Information

Crystallization and structure analysis of the core motif of the Pks13 acyltransferase domain from Mycobacterium tuberculosis.

Publications

Crystallization and structure analysis of the core motif of the Pks13 acyltransferase domain from <i>Mycobacterium tuberculosis</i>.

Similar Datasets

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