4i02

structure of the mutant Catabolite gene activator protein V140A

spinqualitylabelsall models 4i02, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i02 is a 6 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CMP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CRP_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. Publication Abstract from PubMed Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change. The mechanisms, however, for communicating dynamic fluctuations between sites are debated. We provide a foundational theory for how allostery can occur as a function of low-frequency dynamics without a change in structure. We have generated coarse-grained models that describe the protein backbone motions of the CRP/FNR family transcription factors, CAP of Escherichia coli and GlxR of Corynebacterium glutamicum. The latter we demonstrate as a new exemplar for allostery without conformation change. We observe that binding the first molecule of cAMP ligand is correlated with modulation of the global normal modes and negative cooperativity for binding the second cAMP ligand without a change in mean structure. The theory makes key experimental predictions that are tested through an analysis of variant proteins by structural biology and isothermal calorimetry. Quantifying allostery as a free energy landscape revealed a protein "design space" that identified the inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, through analyzing CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. This finding provides a link between the position of CRP/FNR transcription factors within the allosteric free energy landscapes and evolutionary selection pressures. Our study therefore reveals significant features of the mechanistic basis for allostery. Changes in low-frequency dynamics correlate with allosteric effects on ligand binding without the requirement for a defined spatial pathway. In addition to evolving suitable three-dimensional structures, CRP/FNR family transcription factors have been selected to occupy a dynamic space that fine-tunes biological activity and thus establishes the means to engineer allosteric mechanisms driven by low-frequency dynamics. Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors.,Rodgers TL, Townsend PD, Burnell D, Jones ML, Richards SA, McLeish TC, Pohl E, Wilson MR, Cann MJ PLoS Biol. 2013 Sep;11(9):e1001651. doi: 10.1371/journal.pbio.1001651. Epub 2013 , Sep 10. PMID:24058293 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Catabolite gene activator protein 3D structures

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