Das, Satyabrata and Kumar, Parimal and Bhor, Vikrant and Surolia, A and Vijayan, M (2006) Invariance and variability in bacterial PanK: a study based on the crystal structure of Mycobacterium tuberculosis PanK. In: Acta Crystallographica Section D-Biological Crystallography, 62 (6). pp. 628-638.
6.pdf - Published Version
Restricted to Registered users only
Download (2448Kb) | Request a copy
Pantothenate kinase ( PanK) is a ubiquitous and essential enzyme that catalyzes the first step of the universal coenzyme A biosynthetic pathway. In this step, pantothenate ( vitamin B-5) is converted to 4'-phosphopantothenate, which subsequently forms coenzyme A in four enzymatic steps. The complex of this enzyme from Mycobacterium tuberculosis ( MtPanK) with a derivative of the feedback inhibitor coenzyme A has been crystallized in two forms and its structure solved. The structure was refined in both forms using room-temperature and low-temperature X-ray data. In both forms, the MtPanK subunit has a mononucleotide-binding fold with a seven-stranded central beta-sheet and helices on either side. However, there is a small though significant difference in subunit association between the two forms. The structure is also grossly similar to the enzyme from Escherichia coli. The active-site pocket and the dimeric interface are on two opposite sides of the PanK subunit. The enzymes from M. tuberculosis and E. coli exhibit several differences, particularly at the dimeric interface. On the other hand, the coenzyme A-binding region is almost entirely conserved. A delineation of the invariant and variable features of the PanK structure further indicates that the dimeric interface is very variable, while the coenzyme A-binding site is substantially invariant. A sequence alignment involving various bacterial PanKs is in agreement with this conclusion. The strong correlation between structural plasticity, evolutionary conservation and variability and function exhibited by the molecule could be important in the design of species-specific inhibitors of the enzyme.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to International Union of Crystallography.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||30 Mar 2009 10:49|
|Last Modified:||19 Sep 2010 04:57|
Actions (login required)