3i59 | pdb_00003i59

Crystal structure of MtbCRP in complex with N6-cAMP

spinqualitylabelsall models 3i59, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3i59 is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.29Å Ligands: CL, MSE, N6R, N6S Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CRPL_MYCTU Global transcriptional regulator that complexes with cAMP and binds to specific DNA promoter sites, causing DNA-bending, to regulate transcription. cAMP improves binding to specific DNA sequences, probably by altering protein conformation. The CRP regulon is predicted to contain about 115 genes. Some genes are activated by CRP (rpfA, whiB1) while others are repressed (fadD10). There are 2 CRP-binding sites in the promoter of whiB1, at low concentrations of CRP with or without cAMP transcription of whiB1 is enhanced via site CRP1, then repressed as site CRP2 is filled. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The cAMP receptor protein (CRP) from Mycobacterium tuberculosis is a cAMP-responsive global transcriptional regulator, responsible for the regulation of a multitude of diverse proteins. We have determined the crystal structures of the CRP.cAMP and CRP.N(6)-cAMP derivative-bound forms of the enzyme to 2.2- and 2.3 A-resolution, respectively, to investigate cAMP-mediated conformational and structural changes. The allosteric switch from the open, inactive conformation to the closed, active conformation begins with a number of changes in the ligand-binding cavity upon cAMP binding. These subtle structural changes and numerous non-bonding interactions between cAMP, the N-domain residues, and the C-domain helices demonstrate that the N-domain hairpin loop acts as a structural mediator of the allosteric switch. Based on the CRP.N(6)-cAMP crystal structure, binding of N(6)-cAMP with a bulkier methylphenylethyl extension from the N6 atom stabilizes the cAMP-binding domain, N-domain hairpin, and C-terminal domain in a similar manner as that of the CRP.cAMP structure, maintaining structural integrity within the subunits. However, the bulkier N6 extension of N(6)-cAMP (in R conformation) is accommodated only in subunit A with minor changes, whereas in subunit B, the N6 extension is in the S conformation hindering the hinge region of the central helix. As a result, the entire N-domain and the C-domain of subunit B integrated by the cAMP portion of this ligand, together tilt away ( approximately 7 degrees tilt) from central helix C, positioning the helix-turn-helix motif in an unfavorable position for the DNA substrate, asymmetrically. Together, these crystal structures demonstrate the mechanism of action of the cAMP molecule and its role in integrating the active CRP structure. Structural insights into the mechanism of the allosteric transitions of Mycobacterium tuberculosis cAMP receptor protein.,Reddy MC, Palaninathan SK, Bruning JB, Thurman C, Smith D, Sacchettini JC J Biol Chem. 2009 Dec 25;284(52):36581-91. Epub 2009 Sep 9. PMID:19740754 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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