Biochemical and structural studies of mutants indicate concerted movement of the dimer interface and ligand-binding region of Mycobacterium tuberculosis pantothenate kinase.

ABSTRACT: Two point mutants and the corresponding double mutant of Mycobacterium tuberculosis pantothenate kinase have been prepared and biochemically and structurally characterized. The mutants were designed to weaken the affinity of the enzyme for the feedback inhibitor CoA. The mutants exhibit reduced activity, which can be explained in terms of their structures. The crystals of the mutants are not isomorphous to any of the previously analysed crystals of the wild-type enzyme or its complexes. The mycobacterial enzyme and its homologous Escherichia coli enzyme exhibit structural differences in their nucleotide complexes in the dimer interface and the ligand-binding region. In three of the four crystallographically independent mutant molecules the structure is similar to that in the E. coli enzyme

SUBMITTER: Paul A 

PROVIDER: S-EPMC5683034 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature