Glutamine Phosphoribosylpyrophosphate, subunit 1, domain 1
asparagine synthase (glutamine-hydrolysing)
asparagine synthetase (glutamine-hydrolysing)
glutamine-dependent asparagine synthetase
GLU 352;TYR 357;ASP 384(Magnesium-1 binding);ASP 238;ASP 351(Magnesium-2 binding)
Glutamine-dependent asparagine synthetase from leukemia cells. Chloride dependence, mechanism of action, and inhibition.
Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad.
Arginine 30 and asparagine 74 have functional roles in the glutamine dependent activities of Escherichia coli asparagine synthetase B.
Mapping the aspartic acid binding site of Escherichia coli asparagine synthetase B using substrate analogs.
X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-240
Substrate binding is required for assembly of the active conformation of the catalytic site in Ntn amidotransferases: evidence from the 1.8 A crystal structure of the glutaminase domain of glucosamine 6-phosphate synthase.
Mutagenesis and chemical rescue indicate residues involved in beta-aspartyl-AMP formation by Escherichia coli asparagine synthetase B.
Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase.
Kinetic mechanism of Escherichia coli asparagine synthetase B.
Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product.
Characterization of inhibitors acting at the synthetase site of Escherichia coli asparagine synthetase B.
Revisiting the steady state kinetic mechanism of glutamine-dependent asparagine synthetase from Escherichia coli.
This enzyme is composed of two domains, N-terminal glutaminase domain, and C-terminal ligase domain. These domains catalyzes the following reactions: (A) Hydrolysis of glutamine amide (by the N-terminal glutaminase domain) (see [9]): (A#) This domain is homologous to the N-terminal glutaminase domain of Glutamine-fructose-6-phosphate transaminase (T00201 in EzCatDB), and has a similar reaction mechanism to its mechanism. (A1) Nucleophile, Cys1 can be either in an active conformation with the thiol group close to the substrate amide, or in an inactive one with the group pointing away from the substrate. During the catalysis, its conformation must be active. (A2) The N-terminal alpha-amino group acts as a general base, which activates the thiol group of the N-terminal Cys1, through a water molecule. (A3) The activated thiol group attacks the amide carbon of a substrate, glutamine, to form a tetrahedral intermediate. The intermediate is stabilized by an oxyanion hole, made up by mainchain amide groups of Asn74 and Gly75. (A4) The intermediate collapses to form a gamma-glutamylthioester and to release ammonia which might be protonated by the water bound to the alpha-amino group of Cys1. (A5) Another water (distinct from the above bound water) is activated through the bound water by the alpha-amino group. (A6) The activated water makes a nucleophilic attack on the thiolester carbon, to form a tetrahedral intermediate. This intermediate is also stabilized by the oxyanion hole. (A7) The intermediate collapses to release the product, glutamate, from Cys1, and the thiol group is protonated through the bound water. (B) Transfer of adenylate (AMP) to carboxylate oxygen of Aspartate: (C) Transfer of acyl group of Asp-AMP intermediate to ammonia: