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Literature summary extracted from

  • Punkvang, A.; Kamsri, P.; Mulholland, A.; Spencer, J.; Hannongbua, S.; Pungpo, P.
    Simulations of shikimate dehydrogenase from Mycobacterium tuberculosis in complex with 3-dehydroshikimate and NADPH suggest strategies for MtbSDH inhibition (2019), J. Chem. Inf. Model., 59, 1422-1433 .
    View publication on PubMed

Application

EC Number Application Comment Organism
1.1.1.25 drug development the enzyme is a promising target for antituberculosis agent development Mycobacterium tuberculosis

Protein Variants

EC Number Protein Variants Comment Organism
1.1.1.25 A213L site-directed mutagenesis, analysis of substrate and cofactor binding compared to wild-type enzyme Mycobacterium tuberculosis
1.1.1.25 D105N site-directed mutagenesis, analysis of substrate and cofactor binding compared to wild-type enzyme Mycobacterium tuberculosis
1.1.1.25 K69A site-directed mutagenesis, analysis of substrate and cofactor binding compared to wild-type enzyme Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.25 additional information simulations of shikimate dehydrogenase from Mycobacterium tuberculosis in complex with 3-dehydroshikimate and NADPH for MtbSDH inhibition strategy, overview. Rational design of hybrid MtbSDH inhibitors able to bind in both the substrate (DHS) and cofactor (NADPH) pockets Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.25 shikimate + NADP+ Mycobacterium tuberculosis
-
 3-dehydroshikimate + NADPH + H+
-
 r

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.25 Mycobacterium tuberculosis A0A045GU47
-
-
1.1.1.25 no activity in Homo sapiens
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.25 shikimate + NADP+
-
 Mycobacterium tuberculosis 3-dehydroshikimate + NADPH + H+
-
 r

Subunits

EC Number Subunits Comment Organism
1.1.1.25 More the overall structure of SDH comprises two alpha/beta domains linked centrally by two alpha-helices. A deep groove between these two domains contains the active site for the binding of substrate and cofactor Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
1.1.1.25 AroE
-
 Mycobacterium tuberculosis
1.1.1.25 MtbSDH
-
 Mycobacterium tuberculosis
1.1.1.25 SDH
-
 Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.25 NADP+
-
 Mycobacterium tuberculosis
1.1.1.25 NADPH enzyme MtbSDH utilizes NADPH in the proS form, binding structure, overview Mycobacterium tuberculosis

General Information

EC Number General Information Comment Organism
1.1.1.25 metabolism the enzyme is active in the shikimic acid pathway, which is present in bacteria, fungi, plants and in certain apicomplexan parasites but is absent from humans, pathway overview Mycobacterium tuberculosis
1.1.1.25 additional information molecular docking calculations and molecular dynamics (MD) simulations for enzyme-substrate interaction and binding structure analysis, model of DHS/NADPH/MtbSDH ternary complex, wild-type and mutant enzymes, detailed overview. Lys69 plays a dual role, in positioning NADPH and in catalysis. Asp105 plays a crucial role in positioning both the epsilon-amino group of Lys69 and nicotinamide ring of NADPH for MtbSDH catalysis but makes no direct contribution to DHS binding. Ala213 is the selection key for NADPH binding with the nicotinamide ring in the proS, rather than proR, conformation in the MtbSDH complex. Residues Ser18, Thr65, Lys69, Gln243, and Gln247 forming hydrogen bonds to 3-dehydroshikimate (DHS) Mycobacterium tuberculosis
1.1.1.25 physiological function shikimate dehydrogenase (SDH) from Mycobacterium tuberculosis (MtbSDH), encoded by the aroE gene, is essential for viability of Mycobacterium tuberculosis Mycobacterium tuberculosis