Stereochemical aspects of the nucleophilic attack in different classes of L-asparaginases
Abstract
L-Asparaginases hydrolyze L-asparagine to L-aspartate with the release of ammonia. Currently, three completely unrelated structural classes of L-asparaginases are known, further subdivided into five types. In each class, the hydrolysis reaction is thought to proceed via a nucleophilic attack of an activated Thr or Ser residue on the carbonyl Csp2 atom of the substrate amide group. With the possible exception of class 2 L-asparaginases, which function as N-terminal nucleophile (Ntn) hydrolases, the identity of the nucleophilic residue is, or at least has been historically, the subject of some controversy, and even in class 2 this issue may not be so entirely obvious. Structural chemistry has, however, excellent tools to figure out reaction mechanisms, based on the application of Bürgi's structure correlation method (SCM). Its principle allows one to predict the reaction trajectory if sufficient structural (crystallographic) examples of the reagents along the reaction path are known. With respect to the nucleophilic attack on a carbonyl group, the stereochemistry is governed by the nucleophile...electrophile distance and the Bürgi-Dunitz angle, later supplemented with the Flippin-Lodge angle. The latter angle is shown to be a poor parameter and is better replaced by the Herschlag dihedral between the planes of the attacking nucleophile and the attacked electrophile. In structural enzymology, applicability of the SCM principle requires the availability of structural examples of…
Read the paper
Related studies
- A Survey on Knowledge Graphs: Representation, Acquisition, and Applications
- Toxicity of nanomaterials
- The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies
- Halogen bonding (X‐bonding): A biological perspective
- Biofilm formation at the air–liquid interface by the Pseudomonas fluorescens SBW25 wrinkly spreader requires an acetylated form of cellulose
- Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.