Nucleoside monophosphate kinase monophosphates

Vonrhein et al. 1995] Vonrhein, C., Schlauderer, G.J., Schulz, G.E. Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases. Structure 3 (1995) 483-490. 

All of these triphosphates take part in phosphorylations in the cell. Similarly, specific nucleoside monophosphate kinases catalyze the formation of nucleoside diphosphates from the corresponding monophosphates. 

In the preceding sections the conversion of purines and purine nucleosides to purine nucleoside monophosphates has been discussed. The monophosphates of adenosine and guanosine must be converted to their di- and triphosphates for polymerization to RNA, for reduction to 2 -deoxyribonucleoside diphosphates, and for the many other reactions in which they take part. Adenosine triphosphate is produced by oxidative phosphorylation and by transfer of phosphate from 1,3-diphosphoglycerate and phosphopyruvate to adenosine diphosphate. A series of transphosphorylations distributes phosphate from adenosine triphosphate to all of the other nucleotides. Two classes of enzymes, termed nucleoside mono-phosphokinases and nucleoside diphosphokinases, catalyse the formation of the nucleoside di- and triphosphates by the transfer of the terminal phosphoryl group from adenosine triphosphate. Muscle adenylate kinase (myokinase)... 

The synthesis of purine nucleotides (1) starts from IMP. The base it contains, hypoxanthine, is converted in two steps each into adenine or guanine. The nucleoside monophosphates AMP and CMP that are formed are then phos-phorylated by nucleoside phosphate kinases to yield the diphosphates ADP and GDP, and these are finally phosphorylated into the triphosphates ATP and CTP. The nucleoside triphosphates serve as components for RNA, or function as coenzymes (see p. 106). Conversion of the ribonucleotides into deoxyribo-nucleotides occurs at the level of the diphosphates and is catalyzed by nucleoside diphosphate reductase (B). 

NUCLEOSIDE PHOSPHOTRANSFERASE 2 -Deoxynucleoside 5 -monophosphate, NUCLEOSIDE PHOSPHOTRANSFERASE (DEOXY)NUCLEOSIDE MONOPHOSPHATE KINASE... 

Yan, H. Tsai, M.-D. Nucleoside monophosphate kinases structure, mechanism, and substrate specificity. Adv. EnzymoL Relat. Areas Mol. Biol., 73, 103-134 (1999)... 

Strominger, J,L. Heppel, L.A. Maxwell, E.S. Nucleoside monophosphate kinases. Transphosphorilation between adenosine triphosphate and nucleoside monophosphates. Biochim. Biophys. Acta, 32, 412-421 (1959)... 

S Additional information <2, 4> (<4> formation of a ternary complex, addition of substrates is random [5] <2> ATP-mediated induced-fit of LID in CMPKcoli modulated by CMP leading to a closed conformation of the active site, protected from water [15] <4> the UMP-CMP kinase has a relaxed enantiospecificity for the nucleoside monophosphate acceptor site, but it is restricted to D-nucleotides at the donor site [26]) [5, 15, 26]... 

Orengo, A. Maness, P. Pyrimidine nucleoside monophosphate kinase from rat liver and rat Novikoff ascites hepatoma (EC 2.7.4.14). Methods Enzy-mol., 51, 321-331 (1978)... 

Scott, E.M. Wright, R.C. Kinetics and equihbria of pyrimidine nucleoside monophosphate kinase from human erythrocytes. Biochim. Biophys. Acta, 571, 45-54 (1979)... 

Maness, P. Orengo, A. Activation of rat liver pyrimidine nucleoside monophosphate kinase. Biochim. Biophys. Acta, 429, 182-190 (1976)... 

Teng, Y.-S. Chen, S.-H. Scott, C.R. Human erythrocyte pyrimidine nucleoside monophosphate kinase. Partial purification and properties of two allelic gene products. J. Biol. Chem., 251, 4179-4183 (1976)... 

Seagrave, J. Reyes, P. Pyrimidine nucleoside monophosphate kinase from rat bone marrow cells chromatographic, electrophoretic, and sedimentation behavior of active and inactive enzyme forms. Arch. Biochem. Biophys., 247, 76-83 (1986)... 

Kohno, H. Kumagai, H. Tochikura, T. Purification and properties of pyrimidine nucleoside monophosphate kinase from baker s yeast. Agric. Biol. Chem., 47, 19-24 (1983)... 

Bucurenci, N. Sakamoto, H. Briozzo, P. Palibroda, N. Serina, L. Sarfati, R.S. Labesse, G. Briand, G. Danchin, A. Barzu, O. Gilles, A.M. CMP kinase from Escherichia coli is structurally related to other nucleoside monophosphate kinases. J. Biol. Chem., 271, 2856-2862 (1996)... 

Okajima, T. Fukamizo, T. Goto, S. Fukui, T. Tanizawa, K. Exchange of nucleoside monophosphate-binding domains in adenylate kinase and UMP/CMP kinase. J. Biochem., 124, 359-367 (1998)... 

Briozzo, P. Golinelli-Pimpaneau, B. Gilles, A.M. Gaucher, J.R Burlacu-Miron, S. Sakamoto, H. Janin, J. Barzu, O. Structures of Escherichia coli CMP kinase alone and in complex with CDP a new fold of the nucleoside monophosphate binding domain and insights into cytosine nucleotide specificity. Structure, 6, 1517-1527 (1998)... 

ATP also brings about the formation of other nucleoside diphosphates by the action of a class of enzymes called nucleoside monophosphate kinases. These enzymes, which are generally specific for a particular base but nonspecific for the sugar (ribose or de-oxyribose), catalyze the reaction... 

Nucleoside diphosphates (NDP) are synthesized from the corresponding nucleoside monophosphates (NMP) by base-specific nucleoside monophosphate kinases (Figure 22.9). [Note These kinases do not discriminate between ribose or deoxyribose in the substrate.] ATP is generally the source of the transferred phosphate, because it is present in higher concentrations than the other nucleoside triphosphates. Adenylate kinase is particularly active in liver and muscle, where the turnover of energy from ATP is high. Its function is to maintain an equilibrium among AMP, ADP, and ATP. Nucleoside diphosphates and triphosphates are interconverted by nucleoside diphosphate kinase—an enzyme that, unlike the monophosphate kinases, has broad specificity. 

Nucleoside diphosphates (NDP) are synthesized from the corresponding nucleoside monophosphates (NMP) by base-specific nucleoside monophosphate kinases. NDPs and nucleoside triphosphates (NTP) are interconverted by nucleoside diphosphate kinase—an enzyme that, unlike the monophosphate kinases, has broad specificity. 

Figure 2 Synthesis of nucleoside triphosphates (1) Adenylate kinase (EC 2.1 A3, N = A,C,U) or guanylate kinase (EC 2.7.4.8, N = G), or nucleoside monophosphate kinase (EC 2.7.4.4, N = U). (2) Pyruvate kinase (EC 2.7.1.40). NMP, nucleoside monophosphate NDP, nucleoside diphosphate NTP, nucleoside triphosphate. (From Ref. 12.)...

The regeneration system for CMP-NeuAc can be employed both for a2,3-sialyltransferase-catalyzed reactions and for reactions mediated by a2,6-sialyltransferase. The system starts with NeuAc, the glycosyl acceptor, PEP, and catalytic amounts of ATP and CMP. CMP is converted to CDP by nucleoside monophosphate kinase (EC 2.7.4.4 NMK) in the presence of ATP, which is regenerated from the by-product ADP, catalyzed by PK in the presence ol PEP, then to CTP with PEP by PK. The CTP thus formed reacts with NeuAc, catalyzed b>... 

E i a2,6-sialyKransferase E2 nucleoside monophosphate kinase or adenylate kinase E3 pyruvate kinase E4 CMP-NeuAc synthetase E5 pyrophosphatase... 

Adenylate kinase performs the essential function of recovering AMP formed by many enzymatic processes and converting it to ADP (Eq. 6-65) which can be reconverted to ATP by oxidative or substrate level phosphorylation. The enzyme is present in all organisms. In vertebrates different isoenzymes function in the cytosol, mitochondrial intermembrane space, and mitochondrial matrix.862 863 A group of other nucleotide and deoxynucleotide kinases convert nucleoside monophosphates into diphosphates.864 865 Some of them, e.g., uridylate kinase are similar in structure and properties to adenylate kinase.866 867 Another member of the adenylate kinase family is phosphoribulokinase, an important photosynthetic enzyme (see Fig. 17-14, step a).868... 

However, nucleoside diphosphates (NDP) are still expensive substrates, which can be obtained from much more cheaper nucleoside monophosphates (NMP). In this respect we have combined the SuSy-catalyzed cleavage of sucrose with the enzymatic formation of NDPs from NMPs catalyzed by nucleoside monophosphate kinase (NMPK, EC 2.7.4.4) or myokinase (MK, EC 2.7.4.3), including in situ regeneration of ATP with pyruvate kinase (PK, EC 2.7.1.40) (Fig. 20) [272]. Testing the substrate spectrum of four different kinases disclosed that none of them accepted dTMP as substrate [272], However, dUMP was well accepted by NMPK and dUDP-activated glucose could also substitute dTDP-activated glucose as precursor for the synthesis of activated deoxysugars (see below). The excellent enzyme stabilities under synthesis... 

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