Database accession: MF7000559
Name: ADP-ribose pyrophosphatase of (E82Q mutant) with SO4 and Zn
PDB ID: 1v8w
Experimental method: X-ray (1.66 Å)
Assembly: Homodimer
Source organism: Thermus thermophilus
Primary publication of the structure:
Yoshiba S, Ooga T, Nakagawa N, Shibata T, Inoue Y, Yokoyama S, Kuramitsu S, Masui R
Structural insights into the Thermus thermophilus ADP-ribose pyrophosphatase mechanism via crystal structures with the bound substrate and metal.
(2004) J. Biol. Chem. 279: 37163-74
PMID: 15210687
Abstract:
ADP-ribose pyrophosphatase (ADPRase) catalyzes the divalent metal ion-dependent hydrolysis of ADP-ribose to ribose 5'-phosphate and AMP. This enzyme plays a key role in regulating the intracellular ADP-ribose levels, and prevents nonenzymatic ADP-ribosylation. To elucidate the pyrophosphatase hydrolysis mechanism employed by this enzyme, structural changes occurring on binding of substrate, metal and product were investigated using crystal structures of ADPRase from an extreme thermophile, Thermus thermophilus HB8. Seven structures were determined, including that of the free enzyme, the Zn(2+)-bound enzyme, the binary complex with ADP-ribose, the ternary complexes with ADP-ribose and Zn(2+) or Gd(3+), and the product complexes with AMP and Mg(2+) or with ribose 5'-phosphate and Zn(2+). The structural and functional studies suggested that the ADP-ribose hydrolysis pathway consists of four reaction states: bound with metal (I), metal and substrate (II), metal and substrate in the transition state (III), and products (IV). In reaction state II, Glu-82 and Glu-70 abstract a proton from a water molecule. This water molecule is situated at an ideal position to carry out nucleophilic attack on the adenosyl phosphate, as it is 3.6 A away from the target phosphorus and almost in line with the scissile bond.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
ADP-sugar diphosphatase activity ADP-sugar diphosphatase activity
bis(5'-adenosyl)-pentaphosphatase activity bis(5'-adenosyl)-pentaphosphatase activity
guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity
metal ion binding metal ion binding
nucleotide binding nucleotide binding
UDP-sugar diphosphatase activity UDP-sugar diphosphatase activity
Biological process:
nucleoside phosphate metabolic process nucleoside phosphate metabolic process
ribose phosphate metabolic process ribose phosphate metabolic process
Cellular component:
cytosol cytosol
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: ADP-ribose pyrophosphatase
Source organism: Thermus thermophilus
Length: 170 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGRVYYGGVERTYLYRGRILNLALEGRYEIVEHKPAVAVIALREGRMLFVRQMRPAVGLAPLEIPAGLIEPGEDPLEAARRELAEETGLSGDLTYLFSYFVSPGFTDEKTHVFLAENLKEVEAHPDEDEAIEVVWMRPEEALERHQRGEVEFSATGLVGVLYYHAFLRGR
UniProtKB AC: Q84CU3 (positions: 11-168)
Coverage: 92%
Name: ADP-ribose pyrophosphatase
Source organism: Thermus thermophilus
Length: 170 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMGRVYYGGVERTYLYRGRILNLALEGRYEIVEHKPAVAVIALREGRMLFVRQMRPAVGLAPLEIPAGLIEPGEDPLEAARRELAEETGLSGDLTYLFSYFVSPGFTDEKTHVFLAENLKEVEAHPDEDEAIEVVWMRPEEALERHQRGEVEFSATGLVGVLYYHAFLRGR
UniProtKB AC: Q84CU3 (positions: 11-168)
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: NUDIX domain
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
The authors claim that ADP-ribose pyrophosphatase forms a symmetric homodimer, wherein the two catalytic sites are formed by residues of both monomers, requiring dimerization through domain swapping for substrate recognition and catalytic activity (PMID:11323725). E. coli ADPRase elutes as a dimer in gel exclusion chromatography (PMID:11323725). The N-terminal subdomain (residues 1-54) mediates dimerization and is a strong candidate for MSF, while the C-terminal one is a folded Nudix domain. Other structures belonging to the same domain type also show features implying MSF: large relative interface, domain swapping and a lack of the monomeric form in gel filtration experiments (PMID:12906832, PMID:15210687).
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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