4onu
cAMP-binding acyltransferase from Mycobacterium smegmatis, E234A mutant
Structural highlights
FunctionPAT_MYCS2 Catalyzes specifically the acetylation of the epsilon-amino group of a highly conserved lysine residue in acetyl-CoA synthetase (ACS) and of the universal stress protein (USP) MSMEG_4207. Acetylation results in the inactivation of ACS activity and could be important for mycobacteria to adjust to environmental changes.[1] [2] Publication Abstract from PubMedMycobacteria 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. Allostery and Conformational Dynamics in cAMP-binding Acyltransferases.,Podobnik M, Siddiqui N, Rebolj K, Nambi S, Merzel F, Visweswariah SS J Biol Chem. 2014 Jun 6;289(23):16588-16600. Epub 2014 Apr 18. PMID:24748621[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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