2JJH

E243 mutant of M. tuberculosis Rv3290C

Summary for 2JJH

• Entry DOI: 10.2210/pdb2jjh/pdb
• Related: 2JJE 2JJF 2JJG
• Descriptor: L-LYSINE EPSILON AMINOTRANSFERASE, PYRIDOXAL-5'-PHOSPHATE, 2-OXOGLUTARIC ACID, ... (4 entities in total)
• Functional Keywords: rv3290c, transferase, e243a mutant, m. tuberculosis, lysine epsilon aminotransferase, aminotransferase, pyridoxal phosphate
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 1
• Total formula weight: 49404.17

Authors

Tripathi, S.M.,Ramachandran, R. (deposition date: 2008-04-04, release date: 2009-06-30, Last modification date: 2025-04-09)

Primary citation

Tripathi, S.M.,Agarwal, A.,Ramachandran, R.
Mutational Analysis of Mycobacterium Tuberculosis Lysine Epsilon-Aminotransferase and Inhibitor Co-Crystal Structures, Reveals Distinct Binding Modes.
Biochem.Biophys.Res.Commun., 463:154-, 2015

PubMed Abstract: Lysine ɛ-aminotransferase (LAT) converts lysine to α-aminoadipate-δ-semialdehyde in a PLP-mediated reaction. We mutated active-site T330, N328 and E243, and structurally rationalized their properties. T330A and T330S mutants cannot bind PLP and are inactive. N328A although inactive, binds to PLP. E243A retains activity, but binds α-ketoglutarate in a different conformation. We had earlier identified 2-aminomethyl piperidine derivative as a LAT inhibitor. The co-crystal structure reveals that it mimics binding of C5 substrates and exhibits two binding modes. E243, that shields R422 in the apo enzyme, exhibits conformational changes to permit the binding of the inhibitor in one of the binding modes. Structure-based analysis of bound water in the active site suggests optimization strategies for synthesis of improved inhibitors.

PubMed: 26003725
DOI: 10.1016/J.BBRC.2015.05.055

Experimental method

X-RAY DIFFRACTION (2.7 Å)