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Literature summary extracted from

  • Bagatin, M.C.; Pimentel, A.L.; Biavatti, D.C.; Basso, E.A.; Kioshima, E.S.; Seixas, F.A.V.; Gauze, G.F.
    Targeting the homoserine dehydrogenase of Paracoccidioides species for treatment of systemic fungal infections (2017), Antimicrob. Agents Chemother., 61, e00165-17 .
    View publication on PubMedView publication on EuropePMC

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.3 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
-
Paracoccidioides brasiliensis
1.1.1.3 4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
-
Paracoccidioides lutzii
1.1.1.3 Amphotericin B MIC value against strain Pb18 is 0.12 mg/ml Paracoccidioides brasiliensis
1.1.1.3 Amphotericin B MIC value against strain Pb18 is 0.06 mg/ml Paracoccidioides lutzii
1.1.1.3 itraconazole MIC value against strain Pb18 is 0.007 mg/ml Paracoccidioides brasiliensis
1.1.1.3 itraconazole MIC value against strain Pb18 is 0.007 mg/ml Paracoccidioides lutzii
1.1.1.3 additional information molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Synergistic effects of HS1 and HS2 in combination with itraconazole against Paracoccidioides brasiliensis. Zinc1531037 and Zinc52986906 are not inhibitory Paracoccidioides brasiliensis
1.1.1.3 additional information molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 Molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Zinc1531037 and Zinc52986906 are not inhibitory Paracoccidioides lutzii
1.1.1.3 Zinc203432 MIC value is 0.032 mg/ml Paracoccidioides brasiliensis
1.1.1.3 Zinc203432 MIC value is 0.064 mg/ml Paracoccidioides lutzii
1.1.1.3 Zinc273730 MIC value is 0.064 mg/ml Paracoccidioides brasiliensis
1.1.1.3 Zinc273730 MIC value is 0.064. Zinc273730 makes important contacts with Gly215, Tyr216, Thr217, and Glu218 Paracoccidioides lutzii

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.3 L-homoserine + NAD+ Paracoccidioides brasiliensis
-
L-aspartate 4-semialdehyde + NADH + H+
-
?
1.1.1.3 L-homoserine + NAD+ Paracoccidioides lutzii
-
L-aspartate 4-semialdehyde + NADH + H+
-
?
1.1.1.3 L-homoserine + NAD+ Paracoccidioides lutzii Pb01
-
L-aspartate 4-semialdehyde + NADH + H+
-
?
1.1.1.3 L-homoserine + NAD+ Paracoccidioides brasiliensis PB18
-
L-aspartate 4-semialdehyde + NADH + H+
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.3 Paracoccidioides brasiliensis C1G1C3
-
-
1.1.1.3 Paracoccidioides brasiliensis PB18 C1G1C3
-
-
1.1.1.3 Paracoccidioides lutzii C1GTZ6
-
-
1.1.1.3 Paracoccidioides lutzii Pb01 C1GTZ6
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
1.1.1.3 L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+ proposed reaction mechanisms of hydride transfer from L-homoserine in the active site of Paracoccidioides brasiliensis homoserine dehydrogenase (HSD), Glu218 accepts a proton from the hydroxyl group of L-homoserine, which donates a hydride to the nC-4 carbon of NAD+. Lys233, Lys122, and the water molecule at position 374 (Wat374) serve to bind the substrate Paracoccidioides brasiliensis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.3 L-homoserine + NAD+
-
Paracoccidioides brasiliensis L-aspartate 4-semialdehyde + NADH + H+
-
?
1.1.1.3 L-homoserine + NAD+
-
Paracoccidioides lutzii L-aspartate 4-semialdehyde + NADH + H+
-
?
1.1.1.3 L-homoserine + NAD+
-
Paracoccidioides lutzii Pb01 L-aspartate 4-semialdehyde + NADH + H+
-
?
1.1.1.3 L-homoserine + NAD+
-
Paracoccidioides brasiliensis PB18 L-aspartate 4-semialdehyde + NADH + H+
-
?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.3 HSD
-
Paracoccidioides brasiliensis
1.1.1.3 HSD
-
Paracoccidioides lutzii

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.3 NAD+
-
Paracoccidioides brasiliensis
1.1.1.3 NAD+
-
Paracoccidioides lutzii
1.1.1.3 NADH
-
Paracoccidioides brasiliensis
1.1.1.3 NADH
-
Paracoccidioides lutzii

General Information

EC Number General Information Comment Organism
1.1.1.3 evolution enzyme homoserine dehydrogenase (HSD) belongs to the family of oxidoreductases and is essential for the biosynthesis of threonine (Thr), methionine (Met), and lysine (Lys) in the metabolic pathway of fungi and plants Paracoccidioides brasiliensis
1.1.1.3 evolution enzyme homoserine dehydrogenase (HSD) belongs to the family of oxidoreductases and is essential for the biosynthesis of threonine (Thr), methionine (Met), and lysine (Lys) in the metabolic pathway of fungi and plants Paracoccidioides lutzii
1.1.1.3 additional information structure homology modeling of enzyme with bound substrate NAD+ and L-homoserine using the Saccharomyces cerevisiae enzyme (PDB ID 1EBU) as template, binding analysis, overview. The model with the best output is subjected to gradient minimization, redocking, and molecular dynamics simulation Paracoccidioides brasiliensis