Nucleoside monophosphate kinases

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. 

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)... 

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)... 

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... 

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... 

Fig. 20. Enzymatic synthesis of activated glucoses (25,26,28,29) starting from nucleoside monophosphates and sucrose (24). A nucleoside monophosphate kinase (EC 2.7.7.4) or myokinase (EC 2.7.4.3), B sucrose synthase (EC 2.4.1.13)...

Fig. 15-15 The de novo pyrimidine biosynthetic pathway. CAP, carbamoyl phosphate CA-asp, /V-carbamoyl-L-aspartate DHO, L-dihydroorotate Oro, orotate OMP, orotidine 5 -monophosphate. Enzymes (1) carbamoyl phosphate synthetase II (2) aspartate transcarbamoylase (3) dihydroorotase, (4) dihydroorotate dehydrogenase (5) orotate phosphoribosyltransferase (6) OMP decarboxylase (7) nucleoside monophosphate kinase (8) nucleoside diphosphate kinase (9) CTP synthetase.

Transferases Group transfer Nucleoside monophosphate kinase (NMP kinase) 9... 

Nucleoside Monophosphate Kinases Catalyzing Phosphoryl Group Exchange between Nucleotides Without Promoting Hydrolysis... 

Figure 9.45. Phosphoryl Group Transfer by Nucleoside Monophosphate Kinases. These enzymes catalyze the interconversion of a nucleoside triphosphate (here, ATP) and a nucleoside monophosphate (NMP) into two nucleoside diphosphates by the transfer of a phosphoryl group (shown in red).

How is the other major pyrimidine ribonucleotide, cytidine, formed It is synthesized from the uracil base of UMP, but UMP is converted into UTP before the synthesis can take place. Recall that the diphosphates and triphosphates are the active forms of nucleotides in biosynthesis and energy conversions. Nucleoside monophosphates are converted into nucleoside triphosphates in stages. First, nucleoside monophosphates are converted into diphosphates by specific nucleoside monophosphate kinases that utilize ATP as the phosphoryl-group donor (Section 9.4). For example, UMP is phosphorylated to UDP by UMP kinase. 

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