Nucleoside-phosphate kinase

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nucleoside phosphate kinase
EC number2.7.4.4
CAS number9026-50-0
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

In enzymology, a nucleoside-phosphate kinase (EC is an enzyme that catalyzes the chemical reaction[1]

ATP + nucleoside phosphate ADP + nucleoside diphosphate

Thus, the two substrates of this enzyme are ATP and nucleoside monophosphate, whereas its two products are ADP and nucleoside diphosphate.[2][3]

This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with a phosphate group as acceptor.[4] The systematic name of this enzyme class is ATP:nucleoside-phosphate phosphotransferase. This enzyme is also called NMP-kinase, or nucleoside-monophosphate kinase.


A number of crystal structures have been solved for this class of enzymes, revealing that they share a common ATP binding domain. This section of the enzyme is commonly referred to as the P-loop,[5] in reference to its interaction with the phosphoryl groups on ATP. This binding domain also consists of a β sheet flanked by α helices.

The [P-loop] typically has the amino acid sequence of Gly-X-X-X-X-Gly-Lys.[6] Similar sequences are found in many other nucleotide-binding proteins.

Adenylate kinase, an example nucleoside-phosphate kinase, is shown here in both an open, unbound conformation[7] (left) and with the lid domain closed around Ap5A (right). The P-loop is shown here in green while Ap5A is orange.


Metal ion interaction[edit]

To allow for interaction with this class of enzymes, ATP must first bind to a metal ion such as magnesium or manganese.[8] The metal ion forms a complex with the phosphoryl-group, as well as several water molecules.[9] These water molecules then form hydrogen bonds to a conserved aspartate residue on the enzyme.[10]

The metal ion interaction facilitates binding by holding the ATP molecule in a position allowing for specific binding to the active site and by providing additional points for binding between the substrate and the enzyme. This increases the binding energy.

Conformational changes[edit]

Binding of ATP causes the P-loop to move, in turn making the lid domain lower and secure the ATP in place.[11][12] Nucleoside monophosphate binding induces further changes that render the enzyme catalytically capable of facilitating a transfer of the phosphoryl group from ATP to nucleoside monophosphate.[13]

The necessity of these conformational changes prevents the wasteful hydrolysis of ATP.

This enzyme mechanism is an example of catalysis by approximation: the nucleoside-phosphate kinase binds the substrates to bring them together in the correct position for the phosphoryl group to be transferred.

Biological function[edit]

Similar catalytic domains are present in a variety of proteins, including:


When a phylogenetic tree composed of members of the nucleoside-phosphate kinase family was made,[14] it showed that these enzymes had originally diverged from a common ancestor into long and short varieties. This first change was drastic – the three-dimensional structure of the lid domain changed significantly.

Following the evolution of long and short varieties of NMP-kinases, smaller changes in the amino acid sequences resulted in the differentiation of subcellular localization.


  1. ^ Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 6, Academic Press, New York, 1962, p. 139-149.
  2. ^ AYENGAR P, GIBSON DM, SANADI DR (1956). "Transphosphorylations between nucleoside phosphates". Biochim. Biophys. Acta. 21 (1): 86–91. doi:10.1016/0006-3002(56)90096-8. PMID 13363863.
  3. ^ LIEBERMAN I, KORNBERG A, SIMMS ES (1955). "Enzymatic synthesis of nucleoside diphosphates and triphosphates". J. Biol. Chem. 215 (1): 429–40. PMID 14392176.
  4. ^ HEPPEL LA, STROMINGER JL, MAXWELL ES (1959). "Nucleoside monophosphate kinases. II. Transphosphorylation between adenosine monophosphate and nucleoside triphosphates". Biochim. Biophys. Acta. 32: 422–30. doi:10.1016/0006-3002(59)90615-8. PMID 14401179.
  5. ^ Dreusicke, D.; Schulz, G.E. (1986). "The glycine-rich loop of adenylate kinase forms a giant anion hole". FEBS Lett. 208 (2): 301–304. doi:10.1016/0014-5793(86)81037-7. PMID 3023140.
  6. ^ Byeon, L.; Shi, Z.; Tsai, M.D. (1995). "Mechanism of adenylate kinase. The "essential lysine" helps to orient the phosphates and the active site residues to proper conformations". Biochemistry. 34 (10): 3172–3182. doi:10.1021/bi00010a006. PMID 7880812.
  7. ^ Muller, C.W.; Schlauderer, G.J.; Reinstein, J.; Schulz, G.E. (1996). "Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding". Structure. 4 (2): 147–156. doi:10.2210/pdb4ake/pdb. PMID 8805521.
  8. ^ Berg, J.M.; Tymoczko, J.L.; Stryer, L. (2002). Biochemistry. New York: W H Freeman. ISBN 0-7167-3051-0. Retrieved 2016-01-08.
  9. ^ Krishnamurthy, H.; Lou, H.; Kimple, A.; Vieille, C.; Cukier, R.I. (2005). "Associative mechanism for phosphoryl transfer: a molecular dynamics simulation of Escherichia coli adenylate kinase complexed with its substrates". Proteins. 58 (1): 88–100. doi:10.1002/prot.20301. PMID 15521058.
  10. ^ Pai, E.F.; Sachseneheimer, W.; Schirmer, R.H.; Schulz, G.E. (1996). "Substrate positions and induced-fit in crystalline adenylate kinase". J. Mol. Biol. 114 (1): 37–45. doi:10.1016/0022-2836(77)90281-9. PMID 198550.
  11. ^ Muller, C.W.; Schulz, G.E. (1992). "Structure of the complex between adenylate kinase from Escherichia coli and the inhibitor Ap5A at 1.9 A resolution. A model for a catalytic transition state". J. Mol. Biol. 224 (1): 159–177. doi:10.2210/pdb1ake/pdb. PMID 1548697.
  12. ^ Schlauderer, G.J.; Proba, K.; Schulz, G.E. (1996). "Structure of a mutant adenylate kinase ligated with an ATP-analogue showing domain closure over ATP". J. Mol. Biol. 256 (2): 223–227. doi:10.1006/jmbi.1996.0080. PMID 8594191.
  13. ^ Vonrhein, C.; Schlauderer, G.J.; Schulz, G.E. (1995). "Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases". Structure. 3 (5): 483–490. doi:10.1016/s0969-2126(01)00181-2. PMID 7663945.
  14. ^ Fukami-Kobayashi, Kaoru; Nosaka, Michiko; Nakazawa, Atsushi; Gō, Mitiko (1996). "Ancient Divergence of long and short isoforms of adenylate kinase molecular evolution of the nucleoside monophosphate kinase family". FEBS Letters. 385 (3): 214–220. doi:10.1016/0014-5793(96)00367-5. PMID 8647254.