Database accession: MF7000082
Name: MRD
PDB ID: 1kll
Experimental method: X-ray (1.50 Å)
Assembly: Homodimer
Source organism: Streptomyces lavendulae
Primary publication of the structure:
Martin TW, Dauter Z, Devedjiev Y, Sheffield P, Jelen F, He M, Sherman DH, Otlewski J, Derewenda ZS, Derewenda U
Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein.
(2002) Structure 10: 933-42
PMID: 12121648
Abstract:
Mitomycin C (MC) is a potent anticancer agent. Streptomyces lavendulae, which produces MC, protects itself from the lethal effects of the drug by expressing several resistance proteins. One of them (MRD) binds MC and functions as a drug exporter. We report the crystal structure of MRD and its complex with an MC metabolite, 1,2-cis-1-hydroxy-2,7-diaminomitosene, at 1.5 A resolution. The drug is sandwiched by pi-stacking interactions of His-38 and Trp-108. MRD is a dimer. The betaalphabetabetabeta fold of the MRD molecule is reminiscent of methylmalonyl-CoA epimerase, bleomycin resistance proteins, glyoxalase I, and extradiol dioxygenases. The location of the binding site is identical to the ones in evolutionarily related enzymes, suggesting that the protein may have been recruited from a different metabolic pathway.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
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: Mitomycin-binding protein
Source organism: Streptomyces lavendulae
Length: 130 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSARISLFAVVVEDMAKSLEFYRKLGVEIPAEADSAPHTEAVLDGGIRLAWDTVETVRSYDPEWQAPTGGHRFAIAFEFPDTASVDKKYAELVDAGYEGHLKPWNAVWGQRYAIVKDPDGNVVDLFAPLP
UniProtKB AC: O05205 (positions: 3-130)
Coverage: 98%
Name: Mitomycin-binding protein
Source organism: Streptomyces lavendulae
Length: 130 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSARISLFAVVVEDMAKSLEFYRKLGVEIPAEADSAPHTEAVLDGGIRLAWDTVETVRSYDPEWQAPTGGHRFAIAFEFPDTASVDKKYAELVDAGYEGHLKPWNAVWGQRYAIVKDPDGNVVDLFAPLP
UniProtKB AC: O05205 (positions: 3-130)
Coverage: 98%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The VOC superfamily of metalloenzymes is characterized by a three-dimensional domain-swapped arrangement of tandem βαβββ-motifs (PMID:24447055). The original gene duplication event led to the βαβββ tandem structure, which appears to require dimerization for stability. Two different forms of domain-swapped dimers may coexist in solution (PMID:12121648) in which both subunits of the homodimer participate in coordination of each metal ion and formation of the U-shaped active sites in the enzyme (PMID:24004181). The complex is predominantly dimeric in solution (gel filtration) (PMID:12121648).
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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