2JJF: N328a Mutant Of M. Tuberculosis Rv3290c

Lysine varepsilon-aminotransferase (LAT) converts lysine to alpha-aminoadipate-delta-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 alpha-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.
PDB ID: 2JJFDownload
MMDB ID: 74874
PDB Deposition Date: 2008/4/4
Updated in MMDB: 2009/07
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 2JJF: dimeric; determined by author and by software (PQS)
Molecular Components in 2JJF
Label Count Molecule
Proteins (2 molecules)
L-lysine Epsilon Aminotransferase
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB