5CWA
Structure of Anthranilate Synthase Component I (TrpE) from Mycobacterium tuberculosis with inhibitor bound
Replaces: 4PENSummary for 5CWA
| Entry DOI | 10.2210/pdb5cwa/pdb |
| Descriptor | Anthranilate synthase component 1, SULFATE ION, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | lyase, inhibitor, lyase-lyase inhibitor complex, lyase/lyase inhibitor |
| Biological source | Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh) |
| Total number of polymer chains | 1 |
| Total formula weight | 56110.76 |
| Authors | Johnston, J.M.,Bashiri, G.,Evans, G.L.,Lott, J.S.,Baker, E.N. (deposition date: 2015-07-28, release date: 2015-08-12, Last modification date: 2023-09-27) |
| Primary citation | Bashiri, G.,Johnston, J.M.,Evans, G.L.,Bulloch, E.M.,Goldstone, D.C.,Jirgis, E.N.,Kleinboelting, S.,Castell, A.,Ramsay, R.J.,Manos-Turvey, A.,Payne, R.J.,Lott, J.S.,Baker, E.N. Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex. Acta Crystallogr.,Sect.D, 71:2297-2308, 2015 Cited by PubMed Abstract: The tryptophan-biosynthesis pathway is essential for Mycobacterium tuberculosis (Mtb) to cause disease, but not all of the enzymes that catalyse this pathway in this organism have been identified. The structure and function of the enzyme complex that catalyses the first committed step in the pathway, the anthranilate synthase (AS) complex, have been analysed. It is shown that the open reading frames Rv1609 (trpE) and Rv0013 (trpG) encode the chorismate-utilizing (AS-I) and glutamine amidotransferase (AS-II) subunits of the AS complex, respectively. Biochemical assays show that when these subunits are co-expressed a bifunctional AS complex is obtained. Crystallization trials on Mtb-AS unexpectedly gave crystals containing only AS-I, presumably owing to its selective crystallization from solutions containing a mixture of the AS complex and free AS-I. The three-dimensional structure reveals that Mtb-AS-I dimerizes via an interface that has not previously been seen in AS complexes. As is the case in other bacteria, it is demonstrated that Mtb-AS shows cooperative allosteric inhibition by tryptophan, which can be rationalized based on interactions at this interface. Comparative inhibition studies on Mtb-AS-I and related enzymes highlight the potential for single inhibitory compounds to target multiple chorismate-utilizing enzymes for TB drug discovery. PubMed: 26527146DOI: 10.1107/S1399004715017216 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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