Database accession: MF7000232
Name: DR2231
PDB ID: 2yf9
Experimental method: X-ray (1.90 Å)
Assembly: Homodimer
Source organism: Deinococcus radiodurans
Primary publication of the structure:
Gonçalves AMD, de Sanctis D, McSweeney SM
Structural and functional insights into DR2231 protein, the MazG-like nucleoside triphosphate pyrophosphohydrolase from Deinococcus radiodurans.
(2011) J. Biol. Chem. 286: 30691-30705
PMID: 21733847
Abstract:
Deinococcus radiodurans is among the very few bacterial species extremely resistant to ionizing radiation, UV light, oxidizing agents, and cycles of prolonged desiccation. The proteome of D. radiodurans reflects the evolutionary pressure exerted by chronic exposure to (nonradioactive) forms of DNA and protein damage. A clear example of this adaptation is the overrepresentation of protein families involved in the removal of non-canonical nucleoside triphosphates (NTPs) whose incorporation into nascent DNA would promote mutagenesis and DNA damage. The three-dimensional structure of the DR2231 protein has been solved at 1.80 Å resolution. This protein had been classified as an all-α-helical MazG-like protein. The present study confirms that it holds the basic structural module characteristic of the MazG superfamily; two helices form a rigid domain, and two helices form a mobile domain and connecting loops. Contrary to what is known of MazG proteins, DR2231 protein shows a functional affinity with dUTPases. Enzymatic and isothermal calorimetry assays have demonstrated high specificity toward dUTP but an inability to hydrolyze dTTP, a typical feature of dUTPases. Co-crystallization with the product of hydrolysis, dUMP, in the presence of magnesium or manganese cations, suggests similarities with the dUTP/dUDP hydrolysis mechanism reported for dimeric dUTPases. The genome of D. radiodurans encodes for all enzymes required for dTTP synthesis from dCMP, thus bypassing the need of a dUTPase. We postulate that DR2231 protein is not essential to D. radiodurans and rather performs "house-cleaning" functions within the framework of oxidative stress response. We further propose DR2231 protein as an evolutionary precursor of dimeric dUTPases.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
metal ion binding metal ion binding
nucleoside triphosphate diphosphatase activity nucleoside triphosphate diphosphatase activity
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: HAD superfamily Cof-like phosphohydrolase
Source organism: Deinococcus radiodurans
Length: 148 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSDLPCPPTNAERLHEFHRAIGAATPERPTPPPPELLRLRQTLLDEESAEVRAEIDHLLARQAAGEALSAGDLAPLAHELADLLYVTYGALDQLGIDADAVFAEVHRANLSKASGPRRADGKQLKPEGWRPADVRGVIERLQHAPADD
UniProtKB AC: Q9RS96 (positions: 7-143)
Coverage: 92%
Name: HAD superfamily Cof-like phosphohydrolase
Source organism: Deinococcus radiodurans
Length: 148 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSDLPCPPTNAERLHEFHRAIGAATPERPTPPPPELLRLRQTLLDEESAEVRAEIDHLLARQAAGEALSAGDLAPLAHELADLLYVTYGALDQLGIDADAVFAEVHRANLSKASGPRRADGKQLKPEGWRPADVRGVIERLQHAPADD
UniProtKB AC: Q9RS96 (positions: 7-143)
Coverage: 92%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Phosphoribosyl-ATP pyrophosphohydrolase
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
Phosphoribosyl-ATP pyrophosphohydrolases show a very unusual interlaced segment-swapped dimer, which implies that this obligatory dimer assembly is important for their function. Size-exclusion chromatography combined with static light scattering confirmed that the dimer is the major oligomeric state in solution (PMID:20944217). Upon dimer formation, DR2231 helices 2 and 3 from one monomer stack antiparallel to helices 2′ and 3′ of the other monomer, respectively. A stable four-helix bundle is formed in the center. The intertwining of the two hairpin structures produces an extensive subunit-subunit interface (PMID:21733847).
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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