Literature summary extracted from

Grizot, S.; Salem, M.; Vongsouthi, V.; Durand, L.; Moreau, F.; Dohi, H.; Vincent, S.; Escaich, S.; Ducruix, A.
Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with ADP and ADP-2-deoxy-2-fluoro heptose (2006), J. Mol. Biol., 363, 383-394.

Application

EC Number	Application	Comment	Organism
2.4.99.23	medicine	absence of the enzyme results in a truncated lipopolysaccharide associated with the deeprough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria. Thus, the enzyme represents a promising target in antibacterial drug design	Escherichia coli

Crystallization (Commentary)

EC Number	Crystallization (Comment)	Organism
2.4.99.23	crystals of the enzyme are grown at 18°C by the vapor-diffusion, hanging-drop method by mixing equal volumes of protein (4 mg/ml) and reservoir solution (100 mM Hepes (pH 7.0), 15% (w/v) PEG 1500, 100 mM NaCl (and 5 mM DTT in the case of the Se-Met protein)). Crystals grow within a few days as thin plates (0.15 mM x 0.15 mM x 0.050 mM) and belong to the orthorhombic space group P2(1)2(1)2(1) (a = 78 A, b = 88 A, c = 89 A) with two molecules in the asymmetric unit. Determination of the structure of the enzyme alone at 1.9 A resolution, and in complex with either ADP or the non-cleavable analog adenosine 5'-diphospho-2-deoxy-2-fluoro-L-glycero-beta-D-gluco-heptopyranoside (ADP-2-deoxy-2-fluoro-heptose) of the sugar donor at 2.4 A resolution. Both binary complexes offer a close view of the donor subsite and, together with results from site-directed mutagenesis studies, provide evidence for a model of the catalytic mechanism	Escherichia coli

Inhibitors

EC Number	Inhibitors	Comment	Organism	Structure
2.4.99.23	adenosine 5'-diphospho-2-deoxy-2-fluoro-L-glycero-beta-D-gluco-heptopyranoside	competitive inhibitor	Escherichia coli

Natural Substrates/ Products (Substrates)

EC Number	Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2.4.99.23	ADP-L-glycero-beta-D-manno-heptose + (3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->4)-(3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->6)-2-deoxy-3-O-[(3R)-3-(tetradecanoyloxy)tetradecanoyl]-2-[[(3R)-3-(dodecanoyloxy)tetradecanoyl]amino]-4-O-phospho-beta-D-glucopyranosyl-(1->6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[[(3R)-3-hydroxytetradecanoyl]amino]-1-O-phosphono-alpha-D-glucopyranose	Escherichia coli	the enzyme is involved in the synthesis of the inner core region of lipopolysaccharide. It catalyzes the addition of the first L-glycero-D-manno-heptose (heptose) molecule to one 3-deoxy-D-manno-oct-2-ulosonic acid residue of the Kdo2-lipid A molecule. Heptose is an essential component of the lipopolysaccharide core domain. Its absence results in a truncated lipopolysaccharide associated with the deeprough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria	ADP + alpha-L-glycero-D-manno-heptosyl-(1->5)-[(3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->4)]-(3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->6)-2-deoxy-3-O-[(3R)-3-(tetradecanoyloxy)tetradecanoyl]-2-[[(3R)-3-(dodecanoyloxy)tetradecanoyl]amino]-4-O-phospho-beta-D-glucopyranosyl-(1->6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[[(3R)-3-hydroxytetradecanoyl]amino]-1-O-phosphono-alpha-D-glucopyranose	-	?

Organism

EC Number	Organism	UniProt	Comment	Textmining
2.4.99.23	Escherichia coli	P24173	pathogenic strain RS218	-

Substrates and Products (Substrate)

EC Number	Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2.4.99.23	ADP-L-glycero-beta-D-manno-heptose + (3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->4)-(3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->6)-2-deoxy-3-O-[(3R)-3-(tetradecanoyloxy)tetradecanoyl]-2-[[(3R)-3-(dodecanoyloxy)tetradecanoyl]amino]-4-O-phospho-beta-D-glucopyranosyl-(1->6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[[(3R)-3-hydroxytetradecanoyl]amino]-1-O-phosphono-alpha-D-glucopyranose	the enzyme is involved in the synthesis of the inner core region of lipopolysaccharide. It catalyzes the addition of the first L-glycero-D-manno-heptose (heptose) molecule to one 3-deoxy-D-manno-oct-2-ulosonic acid residue of the Kdo2-lipid A molecule. Heptose is an essential component of the lipopolysaccharide core domain. Its absence results in a truncated lipopolysaccharide associated with the deeprough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria	Escherichia coli	ADP + alpha-L-glycero-D-manno-heptosyl-(1->5)-[(3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->4)]-(3-deoxy-alpha-D-manno-oct-2-ulopyranosylonate)-(2->6)-2-deoxy-3-O-[(3R)-3-(tetradecanoyloxy)tetradecanoyl]-2-[[(3R)-3-(dodecanoyloxy)tetradecanoyl]amino]-4-O-phospho-beta-D-glucopyranosyl-(1->6)-2-deoxy-3-O-[(3R)-3-hydroxytetradecanoyl]-2-[[(3R)-3-hydroxytetradecanoyl]amino]-1-O-phosphono-alpha-D-glucopyranose	-	?

Subunits

EC Number	Subunits	Comment	Organism
2.4.99.23	monomer	-	Escherichia coli

Synonyms

EC Number	Synonyms	Comment	Organism
2.4.99.23	waaC	-	Escherichia coli

pH Optimum

EC Number	pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
2.4.99.23	7.5	-	assay at	Escherichia coli

IC50 Value

EC Number	IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
2.4.99.23	0.03	-	pH 7.5, temperature not specified in the publication	Escherichia coli	adenosine 5'-diphospho-2-deoxy-2-fluoro-L-glycero-beta-D-gluco-heptopyranoside

General Information

EC Number	General Information	Comment	Organism
2.4.99.23	physiological function	the enzyme is involved in the synthesis of the inner core region of lipopolysaccharide. It catalyzes the addition of the first L-glycero-D-manno-heptose (heptose) molecule to one 3-deoxy-D-manno-oct-2-ulosonic acid residue of the Kdo2-lipid A molecule. Heptose is an essential component of the lipopolysaccharide core domain. Its absence results in a truncated lipopolysaccharide associated with the deeprough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria	Escherichia coli

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Release 2023.1 (January 2023)