Database accession: MF7000227
Name: SurE (Coxiella burnetii)
PDB ID: 3ty2
Experimental method: X-ray (1.89 Å)
Assembly: Homodimer
Source organism: Coxiella burnetii
Primary publication of the structure:
Franklin MC, Cheung J, Rudolph MJ, Burshteyn F, Cassidy M, Gary E, Hillerich B, Yao ZK, Carlier PR, Totrov M, Love JD
Structural genomics for drug design against the pathogen Coxiella burnetii.
(2015) Proteins 83: 2124-36
PMID: 26033498
Abstract:
Coxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C. burnetii that have great potential as drug targets. We used high-throughput techniques to produce novel crystal structures of 48 of these proteins. We selected one protein, C. burnetii dihydrofolate reductase (CbDHFR), for additional work to demonstrate the value of these structures for structure-based drug design. This enzyme's structure reveals a feature in the substrate binding groove that is different between CbDHFR and human dihydrofolate reductase (hDHFR). We then identified a compound by in silico screening that exploits this binding groove difference, and demonstrated that this compound inhibits CbDHFR with at least 25-fold greater potency than hDHFR. Since this binding groove feature is shared by many other prokaryotes, the compound identified could form the basis of a novel antibacterial agent effective against a broad spectrum of pathogenic bacteria.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
3'-nucleotidase activity 3'-nucleotidase activity
5'-nucleotidase activity 5'-nucleotidase activity
exopolyphosphatase activity exopolyphosphatase activity
metal ion binding metal ion binding
nucleotide binding nucleotide binding
XMP 5'-nucleosidase activity XMP 5'-nucleosidase activity
Biological process: not assigned
Cellular component:
cytoplasm cytoplasm
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: 5'-nucleotidase SurE
Source organism: Coxiella burnetii
Length: 258 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKKTATPKLRLLLSNDDGVYAKGLAILAKTLADLGEVDVVAPDRNRSGASNSLTLNAPLHIKNLENGMISVEGTPTDCVHLAITGVLPEMPDMVVAGINAGPNLGDDVWYSGTVAAAMEGRFLGLPALAVSLGGELFRYYETAAKVVYQLIQRIEKDPLPPSTILNINVPDLPYEELKGFEVTRLGTRHRAEPTIRQIDPRGHPIYWVGAAGPEQDSGPGTDFFAMNHHCVSITPLRVDLTHYEAFDQLASWVKRLEM
UniProtKB AC: Q9KI21 (positions: 8-258)
Coverage: 97%
Name: 5'-nucleotidase SurE
Source organism: Coxiella burnetii
Length: 258 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMKKTATPKLRLLLSNDDGVYAKGLAILAKTLADLGEVDVVAPDRNRSGASNSLTLNAPLHIKNLENGMISVEGTPTDCVHLAITGVLPEMPDMVVAGINAGPNLGDDVWYSGTVAAAMEGRFLGLPALAVSLGGELFRYYETAAKVVYQLIQRIEKDPLPPSTILNINVPDLPYEELKGFEVTRLGTRHRAEPTIRQIDPRGHPIYWVGAAGPEQDSGPGTDFFAMNHHCVSITPLRVDLTHYEAFDQLASWVKRLEM
UniProtKB AC: Q9KI21 (positions: 8-258)
Coverage: 97%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Survival protein SurE
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
Two-state thermal unfolding (PMID:23409101). Domain-swapped dimer with extensive swap region and large dimer interface. Dimeric in solution (gel filtration, DLS).
Chain A:
N/A
Chain B:
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)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
