General Information

Database accession: MF6110001 Original MFIB entry

Name: Nucleoside diphosphate kinase (Dictyostelium discoideum)

PDB ID: 1npk PDBe

Experimental method: X-ray (1.80 Å)

Assembly: Homohexamer

Source organism: Dictyostelium discoideum

Primer 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 PubMed

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.


Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

ATP binding ATP binding GeneOntology

nucleoside diphosphate kinase activity nucleoside diphosphate kinase activity GeneOntology

metal ion binding metal ion binding GeneOntology

Biological process:

dGDP phosphorylation obsolete dGDP phosphorylation GeneOntology

response to bacterium response to bacterium GeneOntology

actin cytoskeleton organization actin cytoskeleton organization GeneOntology

translational elongation translational elongation GeneOntology

G-protein coupled receptor signaling pathway G protein-coupled receptor signaling pathway GeneOntology

negative regulation of exocytosis negative regulation of exocytosis GeneOntology

CTP biosynthetic process CTP biosynthetic process GeneOntology

negative regulation of phagocytosis negative regulation of phagocytosis GeneOntology

negative regulation of pinocytosis negative regulation of pinocytosis GeneOntology

cell growth cell growth GeneOntology

GTP biosynthetic process GTP biosynthetic process GeneOntology

dGTP biosynthetic process from dGDP dGTP biosynthetic process from dGDP GeneOntology

UTP biosynthetic process UTP biosynthetic process GeneOntology

Cellular component:

cytoskeleton cytoskeleton GeneOntology

phagocytic vesicle phagocytic vesicle GeneOntology

plasma membrane plasma membrane GeneOntology

ribosome ribosome GeneOntology

secretory granule secretory granule GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 6 distinct polypeptide molecules

Chains: A, B, C, D, E, F

Notes: Chains B, C, D, E and F were generated from chain A using the biomatrices described in the original PDB file.

Number of unique protein segments: 1


Chain A

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: 2-155) UniProt

UniRef90 AC: UniRef90_P22887 (positions: 2-155) UniRef90

Chain B

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: 2-155) UniProt

UniRef90 AC: UniRef90_P22887 (positions: 2-155) UniRef90

Chain C

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: 2-155) UniProt

UniRef90 AC: UniRef90_P22887 (positions: 2-155) UniRef90

Chain D

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: 2-155) UniProt

UniRef90 AC: UniRef90_P22887 (positions: 2-155) UniRef90

Chain E

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: 2-155) UniProt

UniRef90 AC: UniRef90_P22887 (positions: 2-155) UniRef90

Chain F

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: 2-155) UniProt

UniRef90 AC: UniRef90_P22887 (positions: 2-155) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Evidence level: Direct evidence

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:

None

Chain B:

None

Chain C:

None

Chain D:

None

Chain E:

None

Chain F:

None

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