Crystal Structure Determination And Characterisation Of MPtpA – A Low Molecular Weight Protein Tyrosine Phosphatase From Mycobacterium tuberculosis : The low molecular weight protein tyrosine phosphatase (LMWPTPase), a distinctive class of phosphotyrosine phosphatases, is widely distributed from prokaryotes to eukaryotes. The crystal structure of LMWPTPase of microbial origin has been presented here, the first of its kind, from Mycobacterium tuberculosis. The structures were solved in two crystal forms [MPtpA (A) and MPtpA (B)] at 1.9 Å and 2.5 Å resolutions respectively by Molecular Replacement (MR) method and both contained one molecule per asymmetric unit. The A form of MPtpA crystallised in the orthorhombic system with space group P212121 with cell dimensions of a = 40.82 Å, b = 53.61 Å and c = 68.49 Å. The average mosaicity of the reflections was 0.426°. The B-form of MPtpA crystallised in the space group P212121 with cell dimensions of a = 49.31 Å, b = 53.00 Å and c = 64.15 Å. The average mosaicity of the reflections for MPtpA (B) was 0.816°. The structures are compared with the LMWPTPases of eukaryotes. Though the overall structure resembles that of the eukaryotic LMWPTPases structures, there are significant changes around the active site and the PTP-loop. The variable loop, which forms the wall of the crevice leading to the active site, is conformationally unchanged when compared to mammalian LMWPTPase however differences are observed in the residues involved suggesting their role in influencing different substrate specificity. The single amino acid substitution (Leu12Thr) in the consensus sequence, CTGNICRS, of the PTP-loop as compared to that of mammalian LMWPTPases has a major role in the stabilisation of the PTP-loop. A chloride ion and a glycerol molecule were modelled in the active site where the chloride ion interacts in a similar manner as phosphate with the main chain nitrogens of the PTP-loop. This structural study, in addition to identifying mycobacterial specific features, will also form the basis for exploring the substrate specificities of various bacterial LMWPTPases. M. tuberculosis adopts various measures to escape from the hostile environment of the host cells. MPtpA was found to be active in virulent mycobacterial forms during the phagocytosis process. To ascertain the importance of conserved residues Cys11, Arg17, and Asp126 in the catalytic mechanism of MPtpA, site-directed mutagenesis was performed, namely C11S, R17A, D126A, and D126N. Kinetic characterisation of wild-type and the mutant MPtpAs using para-nitrophenyl phosphate revealed the Key Words: X-ray crystallography; active site; inhibition kinetics; LMWPTPase; site-directed mutagenesis; molecular replacement; MPtpA; Mycobacterium tuberculosis; pNPP; PTP-loop; sodium tungstate; sodium orthovanadate; sodium molybdate.