ABCC8 p.Ala146Val
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PMID: 11171040
[PubMed]
Lemaitre N et al: "Study of the structure-activity relationships for the pyrazinamidase (PncA) from Mycobacterium tuberculosis."
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5
Among them, three mutants (D8G, K96T and S104R) had virtually no activity ( 0.004 unit\mg), five (F13S, T61P, P69L, Y103S and A146V) retained a low level of activity (0.06-0.25 unit\mg) and one (T167L) exhibited a wild-type activity (1.51 units\mg).
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ABCC8 p.Ala146Val 11171040:5:126
status: NEW58 All the mutants harboured a single amino acid substitution located either in the conserved (D8G, F13S, P69L, K96T, Y103S, S104R and A146V) or non-conserved (T61P and T167I) regions identified previously in the M. tuberculosis PncA protein [5].
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ABCC8 p.Ala146Val 11171040:58:132
status: NEW66 The second group contained five mutants, F13S, Y103S, A146V, T61P and P69L, which retained a low level Table 1 PZase activities of wild-type (WT) and PncA mutant proteins AS, active site, defined by the residues located within a 6 A/ sphere from the putative active Cys-138 found at the centre of the catalytic cleft (shown in Figure 2).
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ABCC8 p.Ala146Val 11171040:66:54
status: NEW67 Strain Specific activity (units/mg of protein) Location of the mutated residue in the predicted PncA secondary structure PncA WT* 1.33 - PncA WT† 4.43 - K96T 0.002 β3 (AS) D8G 0.004 Loop connecting β1 and αC (AS) S104R 0.004 Loop connecting β3 and αD (AS) F13S 0.06 Loop connecting β1 and αC (AS) Y103S 0.11 Loop connecting β3 and αD (AS) A146V 0.17 αE T61P 0.21 Loop connecting β2 and β3 P69L 0.25 Loop connecting β2 and β3 T167I 1.51 αF * Reference strain H37Rv.
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ABCC8 p.Ala146Val 11171040:67:400
status: NEW109 The four remaining mutants, T61P, P69L, A146V and T167I, were characterized by the replacement of amino acid residues more distant from Cys-138, but three of them were altered in positions associated with structural elements contributing to the active site, i.e. Ala-146 in the αE helix (Figure 2D) and Thr-61 and Pro-69 in the long loop connecting strands β2 and β3 and holding Trp-68 (Figures 1A and 1B).
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ABCC8 p.Ala146Val 11171040:109:40
status: NEW119 The five mutants F13S, Y103S, A146V, T61P and P69L exhibited a significant decrease in PncA activity (see Table 1).
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ABCC8 p.Ala146Val 11171040:119:30
status: NEW129 The moderate level of activity (0.1-0.2 unit\mg) displayed by the three remaining mutants T61P, P69L and A146V seems to be correlated, in the putative PncA structure, to the location of the corresponding substituted amino acids, which are relatively distant from the active cysteine.
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ABCC8 p.Ala146Val 11171040:129:105
status: NEW