Database accession: MF7000563
Name: NDX2 with MG2+ and ampcpr (Thermus thermophilus HB8)
PDB ID: 2yvp
Experimental method: X-ray (1.66 Å)
Assembly: Homodimer
Source organism: Thermus thermophilus
Primary publication of the structure:
Wakamatsu T, Nakagawa N, Kuramitsu S, Masui R
Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8.
(2008) J. Bacteriol. 190: 1108-17
PMID: 18039767
Abstract:
ADP-ribose (ADPR) is one of the main substrates of Nudix proteins. Among the eight Nudix proteins of Thermus thermophilus HB8, we previously determined the crystal structure of Ndx4, an ADPR pyrophosphatase (ADPRase). In this study we show that Ndx2 of T. thermophilus also preferentially hydrolyzes ADPR and flavin adenine dinucleotide and have determined its crystal structure. We have determined the structures of Ndx2 alone and in complex with Mg2+, with Mg2+ and AMP, and with Mg2+ and a nonhydrolyzable ADPR analogue. Although Ndx2 recognizes the AMP moiety in a manner similar to those for other ADPRases, it recognizes the terminal ribose in a distinct manner. The residues responsible for the recognition of the substrate in Ndx2 are not conserved among ADPRases. This may reflect the diversity in substrate specificity among ADPRases. Based on these results, we propose the classification of ADPRases into two types: ADPRase-I enzymes, which exhibit high specificity for ADPR; and ADPRase-II enzymes, which exhibit low specificity for ADPR. In the active site of the ternary complexes, three Mg2+ ions are coordinated to the side chains of conserved glutamate residues and water molecules. Substitution of Glu90 and Glu94 with glutamine suggests that these residues are essential for catalysis. These results suggest that ADPRase-I and ADPRase-II enzymes have nearly identical catalytic mechanisms but different mechanisms of substrate recognition.
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: MutT/nudix family protein
Source organism: Thermus thermophilus
Length: 182 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSPWERILLEEILSEPVRLVKERVRTHTGRELTYVYRPGPVAASFVLPVTERGTALLVRQYRHPTGKFLLEVPAGKVDEGETPEAAARRELREEVGAEAETLIPLPSFHPQPSFTAVVFHPFLALKARVVTPPTLEEGELLESLELPLTEVYALLAKGEIQDASTALTLFYAEPHLKRLGLL
UniProtKB AC: Q5SJY9 (positions: 1-182)
Coverage: 100%
Name: MutT/nudix family protein
Source organism: Thermus thermophilus
Length: 182 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSPWERILLEEILSEPVRLVKERVRTHTGRELTYVYRPGPVAASFVLPVTERGTALLVRQYRHPTGKFLLEVPAGKVDEGETPEAAARRELREEVGAEAETLIPLPSFHPQPSFTAVVFHPFLALKARVVTPPTLEEGELLESLELPLTEVYALLAKGEIQDASTALTLFYAEPHLKRLGLL
UniProtKB AC: Q5SJY9 (positions: 1-182)
Coverage: 100%
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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