Literature summary for 1.1.1.25 extracted from

Wang, K.; Zhu, M.; Tang, Y.; Liu, J.; Yan, F.; Yu, Z.; Zhu, J.
Integration of virtual screening and susceptibility test to discover active-site subpocket-specific biogenic inhibitors of Helicobacter pylori shikimate dehydrogenase (2019), Int. Microbiol., 22, 69-80 .

Inhibitors

Inhibitors	Comment	Organism
(3E)-3-[2-(4-bromophenyl)hydrazinylidene]piperidine-2,4,6-trione	-	Helicobacter pylori
(4Z)-4-[2-(3-hydroxyphenyl)triazan-1-ylidene]-5-methyl-2-[(piperidin-1-yl)methyl]-2,4-dihydro-3H-pyrazol-3-one	-	Helicobacter pylori
(azepan-1-yl)(3-methyl-4,5-dinitrophenyl)methanone	-	Helicobacter pylori
2,5-dimethyl-1,4-phenylene bis(trifluoroacetate)	-	Helicobacter pylori
2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol	-	Helicobacter pylori
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-1-benzopyran-3-yl 6-deoxy-alpha-L-mannopyranoside	-	Helicobacter pylori
2-(3,4-dihydroxyphenyl)ethyl 6-O-[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]-beta-D-glucopyranoside	-	Helicobacter pylori
3,3,3-trifluoro-N-(2-nitrophenyl)-2-(trifluoromethyl)propanamide	-	Helicobacter pylori
3,5,7-trihydroxy-3'-(4-hydroxy-3-methoxyphenyl)-2'-(hydroxymethyl)-2,3,3',4'-tetrahydro-2'H,4H-[2,6'-bi-1-benzopyran]-4-one	-	Helicobacter pylori
3,5-dihydroxy-4-methylbenzoic acid	-	Helicobacter pylori
3-(3,4-dihydroxyphenyl)-2-[[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]propanoic acid	-	Helicobacter pylori
3-(4-hydroxyphenyl)-4-oxo-4H-1-benzopyran-7-yl hexopyranosiduronic acid	-	Helicobacter pylori
3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 3-formyl-2,4-dihydroxy-6-methylbenzoate	-	Helicobacter pylori
3-[[(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,4,5-trihydroxycyclohexane-1-carboxylic acid	-	Helicobacter pylori
4,4'-methylenebis(2,6-dibromo-3,5-dihydroxybenzoic acid)	-	Helicobacter pylori
4-hydroxy-6-methyl-2-oxo-1-(2-phenylethyl)-1,2-dihydropyridine-3-carbaldehyde	-	Helicobacter pylori
4-[[(E)-(2-ethoxy-6-methyl-4-oxo-2H-1-benzopyran-3(4H)-ylidene)methyl]amino]-2-hydroxybenzoic acid	-	Helicobacter pylori
5-(6-hydroxy-1-benzofuran-2-yl)-2-[(1E)-3-methylbut-1-en-1-yl]benzene-1,3-diol	-	Helicobacter pylori
5-[[5-(4-chlorophenyl)furan-2-yl]methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione	-	Helicobacter pylori
additional information	integrated virtual screening/molecular docking-based virtual screening, and antibacterial test for identification of enzyme inhibitors, screening of ZINC database. The HpSDH active site prefers to accommodate amphipathic and polar inhibitors that consist of an aromatic core as well as a number of oxygen-rich polar/charged substituents such as hydroxyl, carbonyl, and carboxyl groups. Subpockets 1- and 2-specific inhibitors exhibit a generally higher activity than subpocket 3-specific inhibitors. Molecular dynamics simulations revealed an intense nonbonded network of hydrogen bonds, Pi-Pi stacking, and van der Waals contacts at the tightly packed complex interfaces of active-site subpockets with their cognate inhibitors, conferring strong stability and specificity to these complex systems. Binding energetic analysis demonstrates that the identified potent inhibitors can target their cognate subpockets with an effective selectivity over noncognate ones. Determination of MIC values of the compounds against Helicobacter strains ATCC43504 and ATCC700392, and structural and energetic analysis of subpocket-inhibitor interactions, overview	Helicobacter pylori

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
shikimate + NADP+	Helicobacter pylori	-	3-dehydroshikimate + NADPH + H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Helicobacter pylori	Q56S04	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
shikimate + NADP+	-	Helicobacter pylori	3-dehydroshikimate + NADPH + H+	-	r

Subunits

Subunits	Comment	Organism
More	the active subpocket 1 is formed by residues Val8, Ser16, Ser18, Asn63, Val64, Thr65, Lys69, Asn90, Asp105, and Gln237, subpocket 2 by residues Asp105, Ser129, Ala179, Thr180, Ser181, Leu184, Leu208, Tyr210, Gly230, Met233, and Leu234, and subpocket 3 by residues Gly125, Ala126, Gly127, Asn148, Arg149, Ser150, Thr180, Ser181, Ala182, and Pro189	Helicobacter pylori

Synonyms

Synonyms	Comment	Organism
AroE	-	Helicobacter pylori
HpSDH	-	Helicobacter pylori

Cofactor

Cofactor	Comment	Organism	Structure
NADP+	-	Helicobacter pylori
NADPH	-	Helicobacter pylori

General Information

General Information	Comment	Organism
metabolism	shikimate dehydrogenase (HpSDH) is a key enzyme in the shikimate pathway of Helicobacter pylori, which catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate	Helicobacter pylori
additional information	analysis of the catalytic active site in the crystal structure of HpSDH in complex with its substrate NADPH and product shikimate. The site can be divided into three spatially separated subpockets that separately correspond to the binding regions of shikimate, NADPH dihydronicotinamide moiety, and NADPH adenine moiety	Helicobacter pylori