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Information on EC 2.7.4.22 - UMP kinase and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WHK5
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2.7.4.22 UMP kinaseIUBMB Comments
This enzyme is strictly specific for UMP as substrate and is used by prokaryotes in the de novo synthesis of pyrimidines, in contrast to eukaryotes, which use the dual-specificity enzyme UMP/CMP kinase (EC 2.7.4.14) for the same purpose . This enzyme is the subject of feedback regulation, being inhibited by UTP and activated by GTP .
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The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
umpk, ump kinase, uridine monophosphate kinase, uridylate kinase, ump-kinase, umpks, ssumpk, xc1936, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SYSTEMATIC NAME
IUBMB Comments
ATP:UMP phosphotransferase
This enzyme is strictly specific for UMP as substrate and is used by prokaryotes in the de novo synthesis of pyrimidines, in contrast to eukaryotes, which use the dual-specificity enzyme UMP/CMP kinase (EC 2.7.4.14) for the same purpose [2]. This enzyme is the subject of feedback regulation, being inhibited by UTP and activated by GTP [1].
CAS REGISTRY NUMBER
COMMENTARY
9036-23-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[([5-oxo-4-[(2R)-tetrahydrofuran-2-ylmethyl]-4,5-dihydro-1H-1,2,4-triazol-3-yl]sulfanyl)acetyl]piperidine-4-carboxylic acid
-
2-(4-acetyl-3,5-dimethyl-1H-pyrazol-1-yl)-N-[1-(2-methoxybenzyl)-1H-pyrazol-5-yl]acetamide
-
4-[2-amino-4-(4-chlorophenyl)-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]butanoic acid
-
4-[2-amino-4-(4-methoxyphenyl)-7-oxo-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]butanoic acid
-
5-fluoro-UTP
at 0.6mM 5-fluoro-UTP, the enzyme activity is decreased by 40%
5-[(9H-[1,2,4]triazolo[4,3-a]benzimidazol-3-ylsulfanyl)methyl]furan-2-carboxylic acid
hydrogen bonding interactions of ZINC12561276 molecule with the active site residues of Mtb-UMPK homology model, overview
N-benzyl-2-[(2S,3R,4S,5R)-3,4-dihydroxy-5-[[(methylsulfonyl)amino]methyl]tetrahydrofuran-2-yl]-N-methylacetamide
-
additional information
structure-based inhibitor design, inhibitor screening and molecular docking study
-
additional information
-
structure-based inhibitor design, inhibitor screening and molecular docking study
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-fluoro-UTP
below 0.15 mM 5-fluoro-UTP increases the activity of the enzyme by 80%
GMP
much weaker activator (only 30% increase in activity at 2.5 mM)
GMP-4-nitrophenol
much weaker activator (only 50% increase in activity at 1 mM)
GTP
GTP increases the reaction rate by a factor of 3.5, with half-saturation at 0.1 mM
additional information
GMP-PCP and 8-bromo-GTP are ineffective as activators
-
additional information
-
GMP-PCP and 8-bromo-GTP are ineffective as activators
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1
5-bromo-UMP
Ki above 1 mM, wild type enzyme, at pH 7.4 and 30°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the sequence motif Gly76-Gly77-Gly78-Asn79 is specific for bacterial UMPKs and most of the conserved sequences are not present in the eukaryotic UMP/UMP-CMP kinases
physiological function
the allosteric regulation mechanism of the enzyme maintains the balance between synthesis of purine and pyrimidine nucleoside triphosphates
additional information
additional information
homology modeling of Mtb-UMPK on the basis of the crystal structure of Escherichia coli-UMPK, structure-function relationships, molecular dynamics study, active-site modeling of the Mtb-UMPK, overview. Six lead molecules make strong hydrogen bonding interactions with Lys36, Gly39, Gly77, Gly78, Asp97, Ser164, and Thr165 amino acid residues in Mtb-UMPK model
additional information
-
homology modeling of Mtb-UMPK on the basis of the crystal structure of Escherichia coli-UMPK, structure-function relationships, molecular dynamics study, active-site modeling of the Mtb-UMPK, overview. Six lead molecules make strong hydrogen bonding interactions with Lys36, Gly39, Gly77, Gly78, Asp97, Ser164, and Thr165 amino acid residues in Mtb-UMPK model
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
using sodium/potassium tartrate (1.2 M) at pH 7.4 and 10 mM GTP
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D113A
the mutant shows an increased Km value for UMP compared to the wild type enzyme
F81W
the mutant shows an increased Km value for UMP compared to the wild type enzyme
F81W/S96A
the mutant shows a decreased Km value for UMP compared to the wild type enzyme
P139A
the mutant shows a decreased Km value for UMP compared to the wild type enzyme
P139H
the mutant shows a decreased Km value for UMP compared to the wild type enzyme
P139W
the mutant shows a decreased Km value for UMP compared to the wild type enzyme
R150A
the mutant shows a decreased Km value for UMP compared to the wild type enzyme
R82H
the mutant shows an increased Km value for UMP compared to the wild type enzyme and 0.7% of the wild-type specific activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60 - 75
the enzyme shows Tm values of 60°C in the absence of nucleotides and 65°C and 75°C with 1 mM GTP and UTP, respectively
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, in 20 mM phosphate (pH 7.0) and 100 mM NaCl, about 2 months, no apparent loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
TALON resin column chromatography and Superdex 200 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene pyrH or Rv2883c, sequence comparisons and phylogenetic analysis and tree
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme is a potential drug target for developing novel anti-tuberculosis drugs
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Labesse, G.; Benkali, K.; Salard-Arnaud, I.; Gilles, A.M.; Munier-Lehmann, H.
Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation
Nucleic Acids Res.
39
3458-3472
2011
Mycobacterium tuberculosis (P9WHK5), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WHK5)
Arvind, A.; Jain, V.; Saravanan, P.; Mohan, C.G.
Uridine monophosphate kinase as potential target for tuberculosis: from target to lead identification
Interdiscip. Sci. Comput. Life Sci.
5
296-311
2013
Mycobacterium tuberculosis (P9WHK5), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WHK5)
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