SMART: NDK domain annotation

NDK

SMART accession number:	SM00562
Description:	These are enzymes that catalyze nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates. These enzymes play important roles in bacterial growth, signal transduction and pathogenicity.
Interpro abstract (IPR001564):	Nucleoside diphosphate kinases (EC 2.7.4.6) (NDK) are enzymes required for the synthesis of nucleoside triphosphates (NTP) other than ATP. They provide NTPs for nucleic acid synthesis, CTP for lipid synthesis, UTP for polysaccharide synthesis and GTP for protein elongation, signal transduction and microtubule polymerisation. In eukaryotes, there seems to be a small family of NDK isozymes each of which acts in a different subcellular compartment and/or has a distinct biological function. Eukaryotic NDK isozymes are hexamers of two highly related chains (A and B) [(PUBMED:1851158)]. By random association (A6, A5B...AB5, B6), these two kinds of chain form isoenzymes differing in their isoelectric point. NDK are proteins of 17 Kd that act via a ping-pong mechanism in which a histidine residue is phosphorylated, by transfer of the terminal phosphate group from ATP. In the presence of magnesium, the phosphoenzyme can transfer its phosphate group to any NDP, to produce an NTP. NDK isozymes have been sequenced from prokaryotic and eukaryotic sources. It has also been shown [(PUBMED:2175255)] that the Drosophila awd (abnormal wing discs) protein, is a microtubule-associated NDK. Mammalian NDK is also known as metastasis inhibition factor nm23. The sequence of NDK has been highly conserved through evolution. There is a single histidine residue conserved in all known NDK isozymes, which is involved in the catalytic mechanism [(PUBMED:1851158)]. Our signature pattern contains this residue.
GO process:	UTP biosynthetic process (GO:0006228), nucleoside diphosphate phosphorylation (GO:0006165), GTP biosynthetic process (GO:0006183), CTP biosynthetic process (GO:0006241)
GO function:	nucleoside diphosphate kinase activity (GO:0004550), ATP binding (GO:0005524)
Family alignment:	View or

There are 2057 NDK domains in 1928 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with NDK domain is also avaliable.

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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Chakrabarty AM
- Nucleoside diphosphate kinase: role in bacterial growth, virulence, cell signalling and polysaccharide synthesis.
- Mol Microbiol. 1998; 28: 875-82
- Display abstract
- Nucleoside diphosphate kinase (Ndk) is an important enzyme that generates nucleoside triphosphates (NTPs) or their deoxy derivatives by terminal phosphotransfer from an NTP such as ATP or GTP to any nucleoside diphosphate or its deoxy derivative. As NTPs, particularly GTP, are important for cellular macromolecular synthesis and signalling mechanisms, Ndk plays an important role in bacterial growth, signal transduction and pathogenicity. Specific examples of the role of Ndk in regulating growth, NTP formation and cell surface polysaccharide synthesis in two respiratory tract pathogens, Pseudomonas aeruginosa and Mycobacterium tuberculosis, are discussed.
- Postel EH
- NM23-NDP kinase.
- Int J Biochem Cell Biol. 1998; 30: 1291-5
- Display abstract
- NM23 belongs to a large family of structurally and functionally conserved proteins consisting of 4-6 identically folded subunits of approximately 16-20 kDa. These oligomeric proteins exhibit nucleoside diphosphate kinase (NDPK) activity that catalyzes nonsubstrate specific conversions of nucleoside diphosphates to nucleoside triphosphates. Many NM23 proteins bind DNA. In vivo, NM23-NDPKs regulate a diverse array of cellular events including growth and development. They are also implicated in the pathogenesis and metastasis of tumors. The mechanism whereby NM23 regulates gene expression is proposed to entail DNA-binding and subsequent alterations in promoter DNA structure. Accordingly, NM23 has the potential to become a useful reagent for gene manipulations.
- Ogawa K et al.
- Is outer arm dynein intermediate chain 1 multifunctional?
- Mol Biol Cell. 1996; 7: 1895-907
- Display abstract
- The outer arm dynein of sea urchin sperm axoneme contains three intermediate chains (IC1, IC2, and IC3; M(r) 128,000, 98,000, and 74,000, respectively). IC2 and IC3 are members of the WD family; the WD motif is responsible for a protein-protein interaction. We describe here the molecular cloning of IC1. IC1 has a unique primary structure, the N-terminal part is homologous to the sequence of thioredoxin, the middle part consists of three repetitive sequences homologous to the sequence of nucleoside diphosphate kinase, and the C-terminal part contains a high proportion of negatively charged glutamic acid residues. Thus, IC1 is a novel dynein intermediate chain distinct from IC2 and IC3 and may be a multifunctional protein. The thioredoxin-related part of IC1 is more closely related to those of two redox-active Chlamydomonas light chains than thioredoxin. Antibodies were prepared against the N-terminal and middle domains of IC1 expressed as His-tagged proteins in bacteria. These antibodies cross-reacted with some dynein polypeptides (potential homologues of IC1) from distantly related species. We propose here that the three intermediate chains are the basic core units of sperm outer arm dynein because of their ubiquitous existence. The recombinant thioredoxin-related part of IC1 and outer arm dyneins from sea urchin and distantly related species were specifically bound to and eluted from a phenylarsine oxide affinity column with 2-mercaptoethanol, indicating that they contain vicinal dithiols competent to undergo reversible oxidation/reduction.
- delaRosa A, Williams RL, Steeg PS
- Nm23/nucleoside diphosphate kinase: toward a structural and biochemical understanding of its biological functions.
- Bioessays. 1995; 17: 53-62
- Display abstract
- The nm23 gene, a putative metastasis suppressor gene, was originally identified by its reduced expression in highly metastatic K-1735 murine melanoma cell lines, as compared to related, low metastatic melanoma cell lines. Transfection of nm23 cDNA has been reported to suppress malignant progression in Drosophila and mammalian cells. Highly conserved homologues of nm23 have been found in organisms ranging from the prokaryote Myxococcus xanthus to Drosophila, where the gene is involved in normal development and differentiation. The product of the nm23 gene exhibits a nucleoside diphosphate kinase activity, yet the nucleoside diphosphate kinase activity of Nm23 does not correlate with its apparent biological functions. We review recent cellular, genetic, biochemical and X-ray crystallographic data to formulate and evaluate hypotheses concerning the molecular mechanism of nm23 action.
- Morera S et al.
- Adenosine 5'-diphosphate binding and the active site of nucleoside diphosphate kinase.
- Biochemistry. 1994; 33: 459-67
- Display abstract
- The X-ray structure of nucleoside diphosphate kinase (NDP kinase) from the slime mold Dictyostelium discoideum has been determined to 2.2-A resolution and refined to an R-factor of 0.19 with and without bound ADP-Mg2+. The nucleotide binds near His 122, a residue which becomes phosphorylated during the catalytic cycle. The mode of binding is different from that observed in other phosphokinases, and it involves no glycine-rich sequence. The adenine base makes only nonpolar contacts with the protein. It points outside, explaining the lack of specificity of NDP kinase toward the base. The ribose 2'- and 3'-hydroxyls and the pyrophosphate moiety are H-bonded to polar side chains. A Mg2+ ion bridges the alpha- to the beta-phosphate which approaches the imidazole group of His 122 from the N delta side. The geometry at the active site in the ADP-Mg2+ complex suggests a mechanism for catalysis whereby the gamma-phosphate of a nucleoside triphosphate can be transferred onto His 122 with a minimum of atomic motion.
- Dumas C et al.
- X-ray structure of nucleoside diphosphate kinase.
- EMBO J. 1992; 11: 3203-8
- Display abstract
- The X-ray structure of a point mutant of nucleoside diphosphate kinase (NDP kinase) from Dictyostelium discoideum has been determined to 2.2 A resolution. The enzyme is a hexamer made of identical subunits with a novel mononucleotide binding fold. Each subunit contains an alpha/beta domain with a four stranded, antiparallel beta-sheet. The topology is different from adenylate kinase, but identical to the allosteric domain of Escherichia coli ATCase regulatory subunits, which bind mononucleotides at an equivalent position. Dimer contacts between NDP kinase subunits within the hexamer are similar to those in ATCase. Trimer contacts involve a large loop of polypeptide chain that bears the site of the Pro----Ser substitution in Killer of prune (K-pn) mutants of the highly homologous Drosophila enzyme. Properties of Drosophila NDP kinase, the product of the awd developmental gene, and of the human enzyme, the product of the nm23 genes in tumorigenesis, are discussed in view of the three-dimensional structure and of possible interactions of NDP kinase with other nucleotide binding proteins.
Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the NDK domain.

Protein Disease

Nucleoside diphosphate kinase A (P15531) (SMART) OMIM:156490: Neuroblastoma
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Protein	Disease
Nucleoside diphosphate kinase A (P15531) (SMART)	OMIM:156490: Neuroblastoma

3D Structures of NDK domains in PDB

PDB code	Main view	Title
1b4s		Structure of nucleoside diphosphate kinase h122g mutant
1b99		3'-fluoro-uridine diphosphate binding to nucleoside diphosphate kinase
1be4		Nucleoside diphosphate kinase isoform b from bovine retina
1bhn		Nucleoside diphosphate kinase isoform a from bovine retina
1bux		3'-phosphorylated nucleotides binding to nucleoside diphosphate kinase
1ehw		Human nucleoside diphosphate kinase 4
1f3f		Structure of the h122g nucleoside diphosphate kinase / d4t- triphosphate.mg complex
1f6t		Structure of the nucleoside diphosphate kinase/alpha- borano(rp)-tdp.mg complex
1hhq		Role of active site resiude lys16 in nucleoside diphosphate kinase
1hiy		Binding of nucleotides to ndp kinase
1hlw		Structure of the h122a mutant of the nucleoside diphosphate kinase
1jxv		Crystal structure of human nucleoside diphosphate kinase a
1k44		Mycobacterium tuberculosis nucleoside diphosphate kinase
1kdn		Structure of nucleoside diphosphate kinase
1leo		P100s nucleoside diphosphate kinase
1lwx		Azt diphosphate binding to nucleoside diphosphate kinase
1mn7		Ndp kinase mutant (h122g;n119s;f64w) in complex with abazttp
1mn9		Ndp kinase mutant (h122g) complex with rtp
1nb2		Crystal structure of nucleoside diphosphate kinase from bacillus halodenitrificans
1ncl		Thermal stability of hexameric and tetrameric nucleoside, diphosphate kinases
1ndc		X-ray structure of nucleoside diphosphate kinase complexed with dtdp and mg2+ at 2 a resolution
1ndk		X-ray structure of nucleoside diphosphate kinase
1ndl		The awd nucleotide diphosphate kinase from drosophila
1ndp		Adenosine 5'-diphosphate binding and the active site of nucleoside diphosphate kinase
1nhk		Crystal structure of myxococcus xanthus nucleoside diphosphate kinase and its interaction with a nucleotide substrate at 2.0 angstroms resolution
1nlk		Crystal structure of myxococcus xanthus nucleoside diphosphate kinase and its interaction with a nucleotide substrate at 2.0 angstroms resolution
1npk		Refined x-ray structure of dictyostelium nucleoside diphosphate kinase at 1,8 angstroms resolution
1nsk		The crystal structure of a human nucleoside diphosphate kinase, nm23-h2
1nsp		Mechanism of phosphate transfer by nucleoside diphosphate kinase: x-ray structures of a phospho-histidine intermediate of the enzymes from drosophila and dictyostelium
1nsq		Mechanism of phosphate transfer by nucleoside diphosphate kinase: x-ray structures of a phospho-histidine intermediate of the enzymes from drosophila and dictyostelium
1nue		X-ray structure of nm23 human nucleoside diphosphate kinase b complexed with gdp at 2 angstroms resolution
1pae		Nucleoside diphosphate kinase
1pku		Crystal structure of nucleoside diphosphate kinase from rice
1s57		Crystal structure of nucleoside diphosphate kinase 2 from arabidopsis
1s59		Structure of nucleoside diphosphate kinase 2 with bound dgtp from arabidopsis
1s5z		Ndp kinase in complex with adenosine phosphonoacetic acid
1u8w		Crystal structure of arabidopsis thaliana nucleoside diphosphate kinase 1
1ucn		X-ray structure of human nucleoside diphosphate kinase a complexed with adp at 2 a resolution
1w7w		Structure and mutational analysis of a plant mitochondrial nucleoside diphosphate kinase: identification of residues involved in serine phosphorylation and oligomerization.
1wkj		Crystal structure of nucleoside diphosphate kinase from thermus thermophilus hb8
1wkk		Crystal structure of nucleoside diphosphate kinase from thermus thermophilus hb8 in complex with gdp
1wkl		Crystal structure of nucleoside diphosphate kinase from thermus thermophilus hb8 in complex with atp and adp
1xiq		Plasmodium falciparum nucleoside diphosphate kinase b
1xqi		Crystal structure analysis of an ndp kinase from pyrobaculum aerophilum
1zs6		Structure of human nucleoside-diphosphate kinase 3
2az1		Structure of a halophilic nucleoside diphosphate kinase from halobacterium salinarum
2az3		Structure of a halophilic nucleoside diphosphate kinase from halobacterium salinarum in complex with cdp
2b8p		Crystal structure of acanthamoeba polyphaga mimivirus ndk, the first viral nucleoside diphosphate kinase
2b8q		X-ray structure of acanthamoeba ployphaga mimivirus nucleoside diphosphate kinase complexed with tdp
2bef		Crystal structure of ndp kinase complexed with mg, adp, and bef3
2cwk		Crystal structure of nucleotide diphosphate kinase from pyrococcus horikoshii
2dxd		Crystal structure of nucleoside diphosphate kinase in complex with atp analog
2dxe		Crystal structure of nucleoside diphosphate kinase in complex with gdp
2dxf		Crystal structure of nucleoside diphosphate kinase in complex with gtp analog
2dy9		Crystal structure of nucleoside diphosphate kinase in complex with adp
2dya		Crystal structure of complex between adenine nucleotide and nucleoside diphosphate kinase
2hur		Escherichia coli nucleoside diphosphate kinase
2hvd		Human nucleoside diphosphate kinase a complexed with adp
2hve		S120g mutant of human nucleoside diphosphate kinase a complexed with adp
2nck		Crystal structure of myxococcus xanthus nucleoside diphosphate kinase and its interaction with a nucleotide substrate at 2.0 angstroms resolution
2vu5		Crystal structure of pndk from bacillus anthracis
2zua		Crystal structure of nucleoside diphosphate kinase from haloarcula quadrata
3b54		Saccharomyces cerevisiae nucleoside diphosphate kinase
3b6b		Crystal structure of acanthamoeba polyphaga mimivirus nucleoside diphosphate kinase complexed with dgdp
3bbb		Crystal structure of the nm23-h2 transcription factor complex with dinucleotide d(ag)
3bbc		Crystal structure of r88a mutant of the nm23-h2 transcription factor
3bbf		Crystal structure of the nm23-h2 transcription factor complex with gdp
3ddi		Crystal structure of the mimivirus ndk +kpn-n62l-r107g triple mutant complexed with tdp
3dkd		Crystal structure of the mimivirus ndk +kpn-n62l-r107g triple mutant complexed with gdp
3ee3		Crystal structure of acanthamoeba polyphaga mimivirus nucleoside diphosphate kinase complexed with cdp
3eic		X-ray structure of acanthamoeba ployphaga mimivirus nucleoside diphosphate kinase complexed with udp
3ejm		Crystal structure of the mimivirus ndk +kpn mutant complexed with gdp
3elh		X-ray structure of acanthamoeba ployphaga mimivirus nucleoside diphosphate kinase complexed with dudp
3em1		Crystal structure of the mimivirus ndk +kpn-n62l double mutant complexed with dtdp
3emt		Crystal structure of the mimivirus ndk +kpn-r107g double mutant complexed with dgdp
3ena		Crystal structure of the mimivirus ndk +kpn-n62l-r107g triple mutant complexed with dgdp
3etm		Crystal structure of the mimivirus ndk +kpn-n62l-r107g triple mutant complexed with cdp
3evm		Crystal structure of the mimivirus ndk +kpn-n62l-r107g triple mutant complexed with dcdp
3evo		Crystal structure of the mimivirus ndk +kpn mutant complexed with dtdp
3evw		Crystal structure of the mimivirus ndk r107g mutant complexed with dtdp
3fbb		Crystal structure of the mimivirus ndk n62l-r107g double mutant complexed with udp
3fbc		Crystal structure of the mimivirus ndk n62l-r107g double mutant complexed with dtdp
3fbe		Crystal structure of the mimivirus ndk n62l-r107g double mutant complexed with gdp
3fbf		Crystal structure of the mimivirus ndk n62l mutant complexed with dtdp
3fc9		Crystal structure of the mimivirus ndk +kpn-n62l double mutant complexed with cdp
3fcv		Crystal structure of the mimivirus ndk +kpn-n62l-r107g triple mutant complexed with dudp
3fcw		Crystal structure of the mimivirus ndk n62l mutant complexed with udp
3fkb		Structure of ndpk h122g and tenofovir-diphosphate
3g2x		Structure of mimivirus ndk +kpn - n62l double mutant complexed with dtdp
3gp9		Crystal structure of the mimivirus ndk complexed with gdp
3gpa		Crystal structure of the mimivirus ndk n62l mutant complexed with cdp
3js9		Crystal structure of nucleotide diphosphate kinase family protein from babesia bovis

Links (links to other resources describing this domain)
INTERPRO IPR001564