Database accession: MF6110001
Name: Nucleoside diphosphate kinase (Dictyostelium discoideum)
PDB ID: 1npk
Experimental method: X-ray (1.80 Å)
Assembly: Homohexamer
Source organism: Dictyostelium discoideum
Primary publication of the structure:
Moréra S, LeBras G, Lascu I, Lacombe ML, Véron M, Janin J
Refined X-ray structure of Dictyostelium discoideum nucleoside diphosphate kinase at 1.8 A resolution.
(1994) J. Mol. Biol. 243: 873-90
PMID: 7966307
Abstract:
The X-ray structure of the nucleoside diphosphate kinase (NDP kinase) from Dictyostelium discoideum has been refined at 1.8 A resolution from a hexagonal crystal form with a 17 kDa monomer in its asymmetric unit. The atomic model was derived from the previously determined structure of a point mutant of the protein. It contains 150 amino acid residues out of 155, and 95 solvent molecules. The R-factor is 0.196 and the estimated accuracy of the average atomic position, 0.25 A. The Dictyostelium structure is described in detail and compared to those of Drosophila and Myxococcus xanthus NDP kinases. The protein is a hexamer with D3 symmetry. Residues 8 to 138 of each subunit form a globular alpha/beta domain. The four-stranded beta-sheet is antiparallel; its topology is different from other phosphate transfer enzymes, and also from the HPr protein which, like NDP kinase, carries a phosphorylated histidine. The same topology is nevertheless found in several other proteins that bind mononucleotides, RNA or DNA. Strand connections in NDP kinase involve alpha-helices and a 20-residue segment called the Kpn loop. The beta-sheet is regular except for a beta-bulge in edge strand beta 2 and a gamma-turn at residue Ile120 just preceding strand beta 4. The latter may induce strain in the main chain near the active site His122. The alpha 1 beta 2 motif participates in forming dimers within the hexamer, helices alpha 1 and alpha 3, the Kpn loop and C terminus, in forming trimers. The subunit fold and dimer interactions found in Dictyostelium are conserved in other NDP kinases. Trimer interactions probably occur in all eukaryotic enzymes. They are absent in the bacterial Myxococcus xanthus enzyme which is a tetramer, even though the subunit structure is very similar. In Dictyostelium, contacts between Kpn loops near the 3-fold axis block access to a central cavity lined with polar residues and filled with well-defined solvent molecules. Biochemical data on point mutants highlight the contribution of the Kpn loop to protein stability. In Myxococcus, the Kpn loops are on the tetramer surface and their sequence is poorly conserved. Yet, their conformation is maintained and they make a similar contribution to the substrate binding site.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
ATP binding ATP binding
metal ion binding metal ion binding
nucleoside diphosphate kinase activity nucleoside diphosphate kinase activity
Biological process:
actin cytoskeleton organization actin cytoskeleton organization
asexual reproduction asexual reproduction
CTP biosynthetic process CTP biosynthetic process
dGTP biosynthetic process from dGDP dGTP biosynthetic process from dGDP
G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway
GTP biosynthetic process GTP biosynthetic process
negative regulation of exocytosis negative regulation of exocytosis
negative regulation of phagocytosis negative regulation of phagocytosis
negative regulation of pinocytosis negative regulation of pinocytosis
nucleoside triphosphate biosynthetic process nucleoside triphosphate biosynthetic process
response to bacterium response to bacterium
translational elongation translational elongation
UTP biosynthetic process UTP biosynthetic process
Cellular component:
cytoplasm cytoplasm
cytoskeleton cytoskeleton
phagocytic vesicle phagocytic vesicle
plasma membrane plasma membrane
ribosome ribosome
secretory granule secretory granule
Structural annotations of the participating protein chains.Entry contents: 6 distinct polypeptide molecules
Chains: A-2, A-3, A-5, A, A-4, A-6
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Nucleoside diphosphate kinase, cytosolic
Source organism: Dictyostelium discoideum
Length: 155 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSTNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
UniProtKB AC: P22887 (positions: 6-155)
Coverage: 96%
Name: Nucleoside diphosphate kinase, cytosolic
Source organism: Dictyostelium discoideum
Length: 155 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSTNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
UniProtKB AC: P22887 (positions: 6-155)
Coverage: 96%
Name: Nucleoside diphosphate kinase, cytosolic
Source organism: Dictyostelium discoideum
Length: 155 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSTNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
UniProtKB AC: P22887 (positions: 6-155)
Coverage: 96%
Name: Nucleoside diphosphate kinase, cytosolic
Source organism: Dictyostelium discoideum
Length: 155 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSTNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
UniProtKB AC: P22887 (positions: 6-155)
Coverage: 96%
Name: Nucleoside diphosphate kinase, cytosolic
Source organism: Dictyostelium discoideum
Length: 155 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSTNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
UniProtKB AC: P22887 (positions: 6-155)
Coverage: 96%
Name: Nucleoside diphosphate kinase, cytosolic
Source organism: Dictyostelium discoideum
Length: 155 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSTNKVNKERTFLAVKPDGVARGLVGEIIARYEKKGFVLVGLKQLVPTKDLAESHYAEHKERPFFGGLVSFITSGPVVAMVFEGKGVVASARLMIGVTNPLASAPGSIRGDFGVDVGRNIIHGSDSVESANREIALWFKPEELLTEVKPNPNLYE
UniProtKB AC: P22887 (positions: 6-155)
Coverage: 96%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: -
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The hexameric NDP kinase from Dictyostelium discoideum displays one single, irreversible differential scanning calorimetry peak (Tm:62°C) over a broad protein concentration, indicating a single step denaturation. However, the P105G substitution, which affects a loop implicated in subunit contacts, yields a protein that reversibly dissociates to folded monomers at 38°C before the irreversible denaturation occurs (Tm:47°C). These data indicate a “coupling” of the quaternary structure with the tertiary structure in the wild-type, but not in the mutated protein (PMID:8663370).
Chain A:
N/A
Chain A-2:
N/A
Chain A-3:
N/A
Chain A-5:
N/A
Chain A-4:
N/A
Chain A-6:
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). No related structure was found in the MFIB database.
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