4bhp | pdb_00004bhp
A structural model of CAP mutant (T127L and S128I) in cGMP-bound state
Structural highlights
FunctionCRP_ECOLI This protein complexes with cyclic AMP and binds to specific DNA sites near the promoter to regulate the transcription of several catabolite-sensitive operons. The protein induces a severe bend in the DNA. Acts as a negative regulator of its own synthesis as well as for adenylate cyclase (cyaA), which generates cAMP.[1] Publication Abstract from PubMedThe ability to inhibit binding or enzymatic activity is key to preventing aberrant behaviors of proteins. Allosteric inhibition is desirable as it offers several advantages over competitive inhibition, but the mechanisms of action remain poorly understood in most cases. Here we show that allosteric inhibition can be effected by destabilizing a low-populated conformational state that serves as an on-pathway intermediate for ligand binding, without altering the protein's ground-state structure. As standard structural approaches are typically concerned with changes in the ground-state structure of proteins, the presence of such a mechanism can go easily undetected. Our data strongly argue for the routine use of NMR tools suited to detect and characterize transiently formed conformational states in allosteric systems. Structure information on such important intermediates can ultimately result in more efficient design of allosteric inhibitors. Allosteric inhibition through suppression of transient conformational states.,Tzeng SR, Kalodimos CG Nat Chem Biol. 2013 May 5. doi: 10.1038/nchembio.1250. PMID:23644478[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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