Nucleoside-phosphate kinase explained

nucleoside phosphate kinase
Ec Number:2.7.4.4
Cas Number:9026-50-0
Go Code:0050145

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

ATP + nucleoside phosphate

\rightleftharpoons

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.

Structure

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.

Mechanism

Metal ion interaction

To allow for interaction with this class of enzymes, ATP must first bind to a metal ion such as magnesium or manganese.[7] The metal ion forms a complex with the phosphoryl-group, as well as several water molecules.[8] These water molecules then form hydrogen bonds to a conserved aspartate residue on the enzyme.[9]

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

Binding of ATP causes the P-loop to move, in turn making the lid domain lower and secure the ATP in place.[10] [11] 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.[12]

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

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

Evolution

When a phylogenetic tree composed of members of the nucleoside-phosphate kinase family was made,[13] 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.

Notes and References

  1. Book: Boyer PD, Lardy H, Myrback K . The Enzymes . 2nd . 6 . Academic Press . New York . 1962 . 139–149 .
  2. Ayengar P, Gibson DM, Sanadi DR . Transphosphorylations between nucleoside phosphates . Biochimica et Biophysica Acta . 21 . 1 . 86–91 . July 1956 . 13363863 . 10.1016/0006-3002(56)90096-8 .
  3. Lieberman I, Kornberg A, Simms ES . Enzymatic synthesis of nucleoside diphosphates and triphosphates . The Journal of Biological Chemistry . 215 . 1 . 429–40 . July 1955 . 10.1016/S0021-9258(18)66050-8 . 14392176 . free .
  4. Heppel LA, Strominger JL, Maxwell ES . Nucleoside monophosphate kinases. II. Transphosphorylation between adenosine monophosphate and nucleoside triphosphates . Biochimica et Biophysica Acta . 32 . 422–30 . April 1959 . 14401179 . 10.1016/0006-3002(59)90615-8 .
  5. Dreusicke D, Schulz GE . The glycine-rich loop of adenylate kinase forms a giant anion hole . FEBS Letters . 208 . 2 . 301–4 . November 1986 . 3023140 . 10.1016/0014-5793(86)81037-7 . 11786335 .
  6. Byeon L, Shi Z, Tsai MD . Mechanism of adenylate kinase. The "essential lysine" helps to orient the phosphates and the active site residues to proper conformations . Biochemistry . 34 . 10 . 3172–82 . March 1995 . 7880812 . 10.1021/bi00010a006 .
  7. Book: Berg JM, Tymoczko JL, Stryer L . Biochemistry . 2016-01-08 . 2002 . W H Freeman . New York . 0-7167-3051-0 . registration .
  8. Krishnamurthy H, Lou H, Kimple A, Vieille C, Cukier RI . Associative mechanism for phosphoryl transfer: a molecular dynamics simulation of Escherichia coli adenylate kinase complexed with its substrates . Proteins . 58 . 1 . 88–100 . January 2005 . 15521058 . 10.1002/prot.20301 . 20874015 .
  9. Pai EF, Sachsenheimer W, Schirmer RH, Schulz GE . Substrate positions and induced-fit in crystalline adenylate kinase . Journal of Molecular Biology . 114 . 1 . 37–45 . July 1977 . 198550 . 10.1016/0022-2836(77)90281-9 .
  10. Müller CW, Schulz GE . Structure of the complex between adenylate kinase from Escherichia coli and the inhibitor Ap5A refined at 1.9 A resolution. A model for a catalytic transition state . Journal of Molecular Biology . 224 . 1 . 159–77 . March 1992 . 1548697 . 10.2210/pdb1ake/pdb .
  11. Schlauderer GJ, Proba K, Schulz GE . Structure of a mutant adenylate kinase ligated with an ATP-analogue showing domain closure over ATP . Journal of Molecular Biology . 256 . 2 . 223–7 . February 1996 . 8594191 . 10.1006/jmbi.1996.0080 .
  12. Vonrhein C, Schlauderer GJ, Schulz GE . Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases . Structure . 3 . 5 . 483–90 . May 1995 . 7663945 . 10.1016/s0969-2126(01)00181-2 . free .
  13. Fukami-Kobayashi K, Nosaka M, Nakazawa A, Go M . Ancient divergence of long and short isoforms of adenylate kinase: molecular evolution of the nucleoside monophosphate kinase family . FEBS Letters . 385 . 3 . 214–20 . May 1996 . 8647254 . 10.1016/0014-5793(96)00367-5 . 24934783 . free .

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