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Literature summary for 1.1.1.37 extracted from

  • Wang, X.M.; Soetaert, K.; Peirs, P.; Kalai, M.; Fontaine, V.; Dehaye, J.P.; Lefevre, P.
    Biochemical analysis of the NAD+-dependent malate dehydrogenase, a substrate of several serine/threonine protein kinases of Mycobacterium tuberculosis (2015), PLoS ONE, 10, e0123327.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene mdh, overexpression of soluble His6-tagged enzyme in Escherichia coli Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
additional information MDH phosphorylation by PknD inhibits the MDH activity by 40%, phosphorylation by other kinases also inhibits the enzyme activity: 42-53% inhibition for PknF, 23-32% inhibition for PknH, and 27-38% inhibition for PknA Mycobacterium tuberculosis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.08
-
NADH recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
0.13
-
NAD+ recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
0.14
-
oxaloacetate recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
1.04
-
(S)-malate recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-malate + NAD+ Mycobacterium tuberculosis
-
oxaloacetate + NADH + H+
-
r
(S)-malate + NAD+ Mycobacterium tuberculosis H37Rv
-
oxaloacetate + NADH + H+
-
r
additional information Mycobacterium tuberculosis the PknD phosphorylated MDH can bind to Rv1827 and Rv0020c, i.e. glycogen accumulation regulator GarA and protein Fha, two proteins containing a FHA domain. The FHA domain recognizes phosphothreonine on proteins ?
-
?
additional information Mycobacterium tuberculosis H37Rv the PknD phosphorylated MDH can bind to Rv1827 and Rv0020c, i.e. glycogen accumulation regulator GarA and protein Fha, two proteins containing a FHA domain. The FHA domain recognizes phosphothreonine on proteins ?
-
?
oxaloacetate + NADH + H+ Mycobacterium tuberculosis
-
(S)-malate + NAD+
-
r
oxaloacetate + NADH + H+ Mycobacterium tuberculosis H37Rv
-
(S)-malate + NAD+
-
r

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WK13
-
-
Mycobacterium tuberculosis H37Rv P9WK13
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein PknD, one of the eleven eukaryotic-like serine/threonine protein kinases (STPKs) of Mycobacterium tuberculosis, phosphorylates the NAD+-dependent malate dehydrogenase, MDH. PknD phosphorylated the dimeric MDH in vitro. The phosphorylation site is identified on threonine residues and the phosphorylation inhibits the MDH activity, while the presence of the autophosphorylated PknD has no effect by itself on the oxidation of NADH. In vitro, the recombinant MDH can also be phosphorylated by at least five other STPKs, PknA, PknE, PknH, PknJ, and PknG. MDH is hyperphosphorylated in the bacteria at the beginning of the stationary and under oxygen-limited conditions by STPKs other than PknD. On the contrary, when PknD-deficient mutant mycobacteria are grown in a phosphate-depleted medium, MDH is not detectably phosphorylated. Although the MDH is a substrate of several mycobacterial STPKs, the activity of these kinases can depend on the environment, PknD is a key element in the MDH phosphorylation assay under phosphate-poor conditions Mycobacterium tuberculosis

Purification (Commentary)

Purification (Comment) Organism
recombinant soluble His6-tagged enzyme from Escherichia coli by nickel affinity chromatography Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-malate + NAD+
-
Mycobacterium tuberculosis oxaloacetate + NADH + H+
-
r
(S)-malate + NAD+
-
Mycobacterium tuberculosis H37Rv oxaloacetate + NADH + H+
-
r
additional information the PknD phosphorylated MDH can bind to Rv1827 and Rv0020c, i.e. glycogen accumulation regulator GarA and protein Fha, two proteins containing a FHA domain. The FHA domain recognizes phosphothreonine on proteins Mycobacterium tuberculosis ?
-
?
additional information the in vitro conditions to assay the activity of recombinant MDH favors the reduction of oxaloacetate coupled to the oxidation of NADH Mycobacterium tuberculosis ?
-
?
additional information the PknD phosphorylated MDH can bind to Rv1827 and Rv0020c, i.e. glycogen accumulation regulator GarA and protein Fha, two proteins containing a FHA domain. The FHA domain recognizes phosphothreonine on proteins Mycobacterium tuberculosis H37Rv ?
-
?
additional information the in vitro conditions to assay the activity of recombinant MDH favors the reduction of oxaloacetate coupled to the oxidation of NADH Mycobacterium tuberculosis H37Rv ?
-
?
oxaloacetate + NADH + H+
-
Mycobacterium tuberculosis (S)-malate + NAD+
-
r
oxaloacetate + NADH + H+
-
Mycobacterium tuberculosis H37Rv (S)-malate + NAD+
-
r

Subunits

Subunits Comment Organism
homodimer the active form of the Mtb MDH is a dimer. The His6-tag at the N-terminus of recombinant MDH does not inhibit the formation of a dimer by MDH Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
MDH
-
Mycobacterium tuberculosis
NAD+-dependent malate dehydrogenase
-
Mycobacterium tuberculosis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
302
-
(S)-malate recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
320
-
NAD+ recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
2437
-
oxaloacetate recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
3330
-
NADH recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Mycobacterium tuberculosis
NADH
-
Mycobacterium tuberculosis

General Information

General Information Comment Organism
physiological function MDH is an energy-supplying enzyme, that catalyzes the interconversion of malate and oxaloacetate and plays crucial roles in several metabolic pathways including the citric acid cycle. The phosphorylation of enzyme MDH by serine/threonine protein kinases negatively regulates its activity Mycobacterium tuberculosis

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.29
-
(S)-malate recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
2.46
-
NAD+ recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
17.4
-
oxaloacetate recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis
41.6
-
NADH recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis