5KIN

Crystal structure of tryptophan synthase alpha beta complex from Streptococcus pneumoniae

5KIN の概要

• エントリーDOI: 10.2210/pdb5kin/pdb
• 分子名称: Tryptophan synthase alpha chain, Tryptophan synthase beta chain, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: structural genomics, csgid, tryptophan synthase a, tryptophan synthase b, center for structural genomics of infectious diseases, lyase
• 由来する生物種: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 144745.74

構造登録者

Chang, C.,Michalska, K.,Bigelow, L.,Jedrzejczak, R.,ANDERSON, W.F.,JOACHIMIAK, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2016-06-16, 公開日: 2016-07-06, 最終更新日: 2023-11-15)

主引用文献

Michalska, K.,Gale, J.,Joachimiak, G.,Chang, C.,Hatzos-Skintges, C.,Nocek, B.,Johnston, S.E.,Bigelow, L.,Bajrami, B.,Jedrzejczak, R.P.,Wellington, S.,Hung, D.T.,Nag, P.P.,Fisher, S.L.,Endres, M.,Joachimiak, A.
Conservation of the structure and function of bacterial tryptophan synthases.
Iucrj, 6:649-664, 2019

PubMed Abstract: Tryptophan biosynthesis is one of the most characterized processes in bacteria, in which the enzymes from and serve as model systems. Tryptophan synthase (TrpAB) catalyzes the final two steps of tryptophan biosynthesis in plants, fungi and bacteria. This pyridoxal 5'-phosphate (PLP)-dependent enzyme consists of two protein chains, α (TrpA) and β (TrpB), functioning as a linear αββα heterotetrameric complex containing two TrpAB units. The reaction has a complicated, multistep mechanism resulting in the β-replacement of the hydroxyl group of l-serine with an indole moiety. Recent studies have shown that functional TrpAB is required for the survival of pathogenic bacteria in macrophages and for evading host defense. Therefore, TrpAB is a promising target for drug discovery, as its orthologs include enzymes from the important human pathogens , and , the causative agents of pneumonia, legionnaires' disease and tularemia, respectively. However, specific biochemical and structural properties of the TrpABs from these organisms have not been investigated. To fill the important phylogenetic gaps in the understanding of TrpABs and to uncover unique features of TrpAB orthologs to spearhead future drug-discovery efforts, the TrpABs from , and have been characterized. In addition to kinetic properties and inhibitor-sensitivity data, structural information gathered using X-ray crystallo-graphy is presented. The enzymes show remarkable structural conservation, but at the same time display local differences in both their catalytic and allosteric sites that may be responsible for the observed differences in catalysis and inhibitor binding. This functional dissimilarity may be exploited in the design of species-specific enzyme inhibitors.

PubMed: 31316809
DOI: 10.1107/S2052252519005955

実験手法

X-RAY DIFFRACTION (2.45 Å)