Database accession: MF7000716
Name: L34A CzrA in the Zn(II)bound state
PDB ID: 6cda
Experimental method: X-ray (2.00 Å)
Assembly: Homodimer
Source organism: Staphylococcus aureus
Primary publication of the structure:
Capdevila DA, Edmonds KA, Campanello GC, Wu H, Gonzalez-Gutierrez G, Giedroc DP
Functional Role of Solvent Entropy and Conformational Entropy of Metal Binding in a Dynamically Driven Allosteric System.
(2018) J. Am. Chem. Soc. 140: 9108-9119
PMID: 29953213
Abstract:
Allostery is a regulatory phenomenon whereby ligand binding to one site influences the binding of the same or a different ligand to another site on a macromolecule. The physical origins of allosteric regulation remain under intense investigation. In general terms, ligand-induced structural changes, perturbations of residue-specific dynamics, and surrounding solvent molecules all potentially contribute to the global energetics of allostery. While the role of solvent is generally well understood in regulatory events associated with major protein structural rearrangements, the degree to which protein dynamics impact solvent degrees of freedom is unclear, particularly in cases of dynamically driven allostery. With the aid of new crystal structures, extensive calorimetric and residue-specific dynamics studies over a range of time scales and temperatures, we dissect for the first time the relative degree to which changes in solvent entropy and residue-specific dynamics impact dynamically driven, allosteric inhibition of DNA binding by Zn in the zinc efflux repressor, CzrA (chromosomal zinc-regulated repressor). We show that non-native residue-specific dynamics in allosterically impaired CzrA mutants are accompanied by significant perturbations in solvent entropy that cannot be predicted from crystal structures. We conclude that functional dynamics are not necessarily restricted to protein residues but involve surface water molecules that may be responding to ligand (Zn)-mediated perturbations in protein internal motions that define the conformational ensemble, rather than major structural rearrangements.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA binding DNA binding
DNA-binding transcription factor activity DNA-binding transcription factor activity
identical protein binding identical protein binding
metal ion binding metal ion binding
Biological process: not assigned
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Transcriptional regulator
Source organism: Staphylococcus aureus
Length: 106 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSEQYSEINTDTLERVTEIFKALGDYNRIRIMELLSVSEASVGHISHQLNLSQSNVSHQLKLLKSVHLVKAKRQGQSMIYSLDDIHVATMLKQAIHHANHPKESGL
UniProtKB AC: O85142 (positions: 8-102)
Coverage: 89%
Name: Transcriptional regulator
Source organism: Staphylococcus aureus
Length: 106 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSEQYSEINTDTLERVTEIFKALGDYNRIRIMELLSVSEASVGHISHQLNLSQSNVSHQLKLLKSVHLVKAKRQGQSMIYSLDDIHVATMLKQAIHHANHPKESGL
UniProtKB AC: O85142 (positions: 8-102)
Coverage: 89%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Winged helix DNA-binding domain (ArsR family) transcriptional regulator
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
The N-terminal portion of the ArsR family transcriptional regulator, Mj223, is a helix-turn-helix (HTH) winged-helix DNA-binding motif. The C-terminal region of the protein is composed of two leucine-rich α-helices (H5 and H6) that form an antiparallel four-helix bundle with a large, hydrophobic interaction surface on dimerization that forms the hydrophobic core of the dimer (PMID:12471609, PMID:9466913). The C-terminal dimerization subdomain is a nice case of MSF. The protein is a dimer in solution (Dynamic light scattering) (PMID:12471609).
Chain A:
N/A
Chain A-2:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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