5KIN

Crystal structure of tryptophan synthase alpha beta complex from Streptococcus pneumoniae

Summary for 5KIN

• Entry DOI: 10.2210/pdb5kin/pdb
• Descriptor: Tryptophan synthase alpha chain, Tryptophan synthase beta chain, GLYCEROL, ... (4 entities in total)
• Functional Keywords: structural genomics, csgid, tryptophan synthase a, tryptophan synthase b, center for structural genomics of infectious diseases, lyase
• Biological source: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4); More
• Total number of polymer chains: 4
• Total formula weight: 144745.74

Authors

Chang, C.,Michalska, K.,Bigelow, L.,Jedrzejczak, R.,ANDERSON, W.F.,JOACHIMIAK, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2016-06-16, release date: 2016-07-06, Last modification date: 2023-11-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.45 Å)