3HQJ

Structure-function analysis of Mycobacterium tuberculosis acyl carrier protein synthase (AcpS).

3HQJ の概要

• エントリーDOI: 10.2210/pdb3hqj/pdb
• 分子名称: Holo-[acyl-carrier-protein] synthase, MAGNESIUM ION, COENZYME A, ... (4 entities in total)
• 機能のキーワード: an/fold, structural genomics, israel structural proteomics center, ispc, cytoplasm, fatty acid biosynthesis, lipid synthesis, magnesium, metal-binding, transferase
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cytoplasm (By similarity): P0A4W8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14952.39

構造登録者

Dym, O.,Albeck, S.,Peleg, Y.,Schwarz, A.,Shakked, Z.,Burstein, Y.,Zimhony, O.,Israel Structural Proteomics Center (ISPC) (登録日: 2009-06-07, 公開日: 2009-09-15, 最終更新日: 2023-09-06)

主引用文献

Dym, O.,Albeck, S.,Peleg, Y.,Schwarz, A.,Shakked, Z.,Burstein, Y.,Zimhony, O.
Structure-function analysis of the acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis.
J.Mol.Biol., 393:937-950, 2009

PubMed Abstract: We have solved the crystal structure of the acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) at 1.95 A resolution. AcpS, a 4-phosphopantetheinyl transferase, activates two distinct acyl carrier proteins (ACPs) that are present in fatty acid synthase (FAS) systems FAS-I and FAS-II, the ACP-I domain and the mycobacterial ACP-II protein (ACPM), respectively. Mtb, the causal agent of tuberculosis (TB), and all other members of the Corynebacterineae family are unique in possessing both FAS systems to produce and to elongate fatty acids to mycolic acids, the hallmark of mycobacterial cell wall. Various steps in this process are prime targets for first-line anti-TB agents. A comparison of the Mtb AcpS structure determined here with those of other AcpS proteins revealed unique structural features in Mtb AcpS, namely, the presence of an elongated helix followed by a flexible loop and a moderately electronegative surface unlike the positive surface common to other AcpSs. A structure-based sequence comparison between AcpS and its ACP substrates from various species demonstrated that the proteins of the Corynebacterineae family display high sequence conservation, forming a segregated subgroup of AcpS and ACPs. Analysis of the putative interactions between AcpS and ACPM from Mtb, based on a comparison with the complex structure from Bacillus subtilis, showed that the Mtb AcpS and ACPM lack the electrostatic complementarity observed in B. subtilis. Taken together, the common characteristic of the Corynebacterineae family is likely reflected in the participation of different residues and interactions used for binding the Mtb AcpS to ACP-I and ACPM. The distinct features and essentiality of AcpS, as well as the mode of interaction with ACPM and ACP-I in Mtb, could be exploited for the design of AcpS inhibitors, which, similarly to other inhibitors of fatty acid synthesis, are expected to be effective anti-TB-specific drugs.

PubMed: 19733180
DOI: 10.1016/j.jmb.2009.08.065

実験手法

X-RAY DIFFRACTION (1.95 Å)