ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

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

Paul, A and Kumar, P and Surolia, A and Vijayan, M (2017) Biochemical and structural studies of mutants indicate concerted movement of the dimer interface and ligand-binding region of Mycobacterium tuberculosis pantothenate kinase. In: ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 73 (11). pp. 635-643.

[img] PDF
ACT_CRY_SEC_73_635_2017.pdf - Published Version
Restricted to Registered users only

Download (1MB) | Request a copy
Official URL: http://doi.org/10.1107/S2053230X17015667

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. Although the mutants involve changes in the CoA-binding region, the dimer interface and the ligand-binding region move in a concerted manner, an observation which might be important in enzyme action. This work demonstrates that the structure of the mycobacterial enzyme can be transformed into a structure similar to that of the E. coli enzyme through minor perturbations without external influences such as those involving ligand binding.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the INT UNION CRYSTALLOGRAPHY, 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 24 Nov 2017 09:56
Last Modified: 24 Nov 2017 09:56
URI: http://eprints.iisc.ac.in/id/eprint/58301

Actions (login required)

View Item View Item