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Allostery and Conformational Dynamics in cAMP-binding Acyltransferases

Podobnik, Marjetka and Siddiqui, Nida and Rebolj, Katja and Nambi, Subhalaxmi and Merzel, Franci and Visweswariah, Sandhya S (2014) Allostery and Conformational Dynamics in cAMP-binding Acyltransferases. In: JOURNAL OF BIOLOGICAL CHEMISTRY, 289 (23). pp. 16588-16600.

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Official URL: http://dx.doi.org/10.1074/jbc.M114.560086


Mycobacteria harbor unique proteins that regulate protein lysine acylation in a cAMP-regulated manner. These lysine acyltransferases from Mycobacterium smegmatis (KATms) and Mycobacterium tuberculosis (KATmt) show distinctive biochemical properties in terms of cAMP binding affinity to the N-terminal cyclic nucleotide binding domain and allosteric activation of the C-terminal acyltransferase domain. Here we provide evidence for structural features in KATms that account for high affinity cAMP binding and elevated acyltransferase activity in the absence of cAMP. Structure-guided mutational analysis converted KATms from a cAMP-regulated to a cAMP-dependent acyltransferase and identified a unique asparagine residue in the acyltransferase domain of KATms that assists in the enzymatic reaction in the absence of a highly conserved glutamate residue seen in Gcn5-related N-acetyltransferase-like acyltransferases. Thus, we have identified mechanisms by which properties of similar proteins have diverged in two species of mycobacteria by modifications in amino acid sequence, which can dramatically alter the abundance of conformational states adopted by a protein.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 14 Aug 2014 10:11
Last Modified: 14 Aug 2014 10:11
URI: http://eprints.iisc.ac.in/id/eprint/49554

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