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Literature summary for 1.1.1.34 extracted from

  • Dinesh, N.; Pallerla, D.S.R.; Kaur, P.K.; Babu, N.K.; Singh, S.
    Exploring Leishmania donovani 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) as a potential drug target by biochemical, biophysical and inhibition studies (2014), Microb. Pathog., 66, 14-23.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
gene HMGR, DNA and amino acid sequence determination and analysis, sequence comparisons, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) Leishmania donovani

Inhibitors

Inhibitors Comment Organism Structure
atorvastatin inhibits the cell growth as well as the activity of recombinant enzyme, 315.5 nM are enough to cause 50% recombinant LdHMGR enzyme inhibition, 93.2% inhibition at 0.001 mM Leishmania donovani
additional information exogenous supplementation of ergosterol in case of atorvastatin and resveratrol treated cells causes complete reversal of growth inhibition whereas simvastatin is ergosterol refractory Leishmania donovani
resveratrol inhibits the cell growth as well as the activity of recombinant enzyme. Resveratrol shows antitrypanosomal activity with an IC50 value of 0.00013 mM and moderate antipromastigote activity against Leishmania major with IC50 value: 0.153 mM Leishmania donovani
simvastatin inhibits the cell growth as well as the activity of recombinant enzyme, 63% inhibition at 0.1 mM Leishmania donovani

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information kinetic analysis Leishmania donovani
0.0357
-
(R,S)-3-hydroxy-3-methylglutaryl-CoA pH 7.2, 37°C Leishmania donovani
0.07
-
NADPH pH 7.2, 37°C Leishmania donovani

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
45000
-
-
Leishmania donovani

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(R)-mevalonate + CoA + 2 NADP+ Leishmania donovani
-
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
-
r
(R)-mevalonate + CoA + 2 NADP+ Leishmania donovani MHOM/80/IN/Dd8
-
(S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
-
r

Organism

Organism UniProt Comment Textmining
Leishmania donovani I7CKJ5
-
-
Leishmania donovani MHOM/80/IN/Dd8 I7CKJ5
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography Leishmania donovani

Source Tissue

Source Tissue Comment Organism Textmining
cell culture
-
Leishmania donovani
-
promastigote
-
Leishmania donovani
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(R)-mevalonate + CoA + 2 NADP+
-
Leishmania donovani (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
-
r
(R)-mevalonate + CoA + 2 NADP+
-
Leishmania donovani MHOM/80/IN/Dd8 (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
-
r
(R,S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
-
Leishmania donovani (R)-mevalonate + CoA + 2 NADP+
-
r
(R,S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
-
Leishmania donovani MHOM/80/IN/Dd8 (R)-mevalonate + CoA + 2 NADP+
-
r

Subunits

Subunits Comment Organism
? x * 45000, sequence calculation Leishmania donovani
More the secondary structure of LdHMGR confirms the presence of 25.7% alpha helicity Leishmania donovani

Synonyms

Synonyms Comment Organism
3-hydroxy-3-methylglutaryl coenzyme A reductase
-
Leishmania donovani
HMG-CoA reductase
-
Leishmania donovani
HMGR
-
Leishmania donovani

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
-
Leishmania donovani

Temperature Range [°C]

Temperature Minimum [°C] Temperature Maximum [°C] Comment Organism
15 55 19% of maximal activity at 15°C and 29% at 55°C Leishmania donovani

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
90
-
the enzyme retains 60% helical structure Leishmania donovani

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.2
-
-
Leishmania donovani

pH Range

pH Minimum pH Maximum Comment Organism
5.5 10 19% of maximal activity at pH 5.5 and 29% at pH 10.0 Leishmania donovani

Cofactor

Cofactor Comment Organism Structure
NADP+
-
Leishmania donovani
NADPH dependent on Leishmania donovani

pI Value

Organism Comment pI Value Maximum pI Value
Leishmania donovani sequence calculation
-
7.4

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0194
-
pH 7.2, 37°C Leishmania donovani atorvastatin
0.0732
-
pH 7.2, 37°C Leishmania donovani simvastatin

General Information

General Information Comment Organism
metabolism rate limiting enzyme of the ergosterol biosynthetic pathway Leishmania donovani