2BPQ

Anthranilate phosphoribosyltransferase (TrpD) from Mycobacterium tuberculosis (Apo structure)

2BPQ の概要

• エントリーDOI: 10.2210/pdb2bpq/pdb
• 分子名称: ANTHRANILATE PHOSPHORIBOSYLTRANSFERASE, BENZAMIDINE, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: transferase, tryptophan biosynthesis, anthranilate, transferase phosphoribosyltransferase, amino-acid biosynthesis, aromatic amino acid biosynthesis, glycosyltransferase, psi, protein structure initiative, tb structural genomics consortium, tbsgc, structural genomics
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76546.63

構造登録者

Lee, C.E.,Goodfellow, C.,Javid-Majd, F.,Baker, E.N.,Lott, J.S.,TB Structural Genomics Consortium (TBSGC) (登録日: 2005-04-22, 公開日: 2006-01-04, 最終更新日: 2024-05-08)

主引用文献

Lee, C.E.,Goodfellow, C.,Javid-Majd, F.,Baker, E.N.,Lott, J.S.
The Crystal Structure of Trpd, a Metabolic Enzyme Essential for Lung Colonization by Mycobacterium Tuberculosis, in Complex with its Substrate Phosphoribosylpyrophosphate
J.Mol.Biol., 355:784-, 2006

PubMed Abstract: Mycobacterium tuberculosis, the cause of tuberculosis, presents a major threat to human health worldwide. Biosynthetic enzymes that are essential for the survival of the bacterium, especially in activated macrophages, are important potential drug targets. Although the tryptophan biosynthesis pathway is thought to be non-essential for many pathogens, this appears not to be the case for M.tuberculosis, where a trpD gene knockout fails to cause disease in mice. We therefore chose the product of the trpD gene, anthranilate phosphoribosyltransferase, which catalyses the second step in tryptophan biosynthesis, for structural analysis. The structure of TrpD from M.tuberculosis was solved by X-ray crystallography, at 1.9 A resolution for the native enzyme (R = 0.191, Rfree = 0.230) and at 2.3 A resolution for the complex with its substrate phosphoribosylpyrophosphate (PRPP) and Mg2+ (R = 0.194, Rfree = 0.255). The enzyme is folded into two domains, separated by a hinge region. PRPP binds in the C-terminal domain, together with a pair of Mg ions. In the substrate complex, two flexible loops change conformation compared with the apo protein, to close over the PRPP and to complete an extensive network of hydrogen-bonded interactions. A nearby pocket, adjacent to the hinge region, is postulated by in silico docking as the binding site for anthranilate. A bound molecule of benzamidine, which was essential for crystallization and is also found in the hinge region, appears to reduce flexibility between the two domains.

PubMed: 16337227
DOI: 10.1016/J.JMB.2005.11.016

実験手法

X-RAY DIFFRACTION (1.9 Å)