3B9G

Crystal structure of loop deletion mutant of Trypanosoma vivax nucleoside hydrolase (3GTvNH) in complex with ImmH

Summary for 3B9G

• Entry DOI: 10.2210/pdb3b9g/pdb
• Related: 1HOZ 1HPO 1KIC 1KIE 1R4F 2MAS
• Descriptor: IAG-nucleoside hydrolase, CALCIUM ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: rossmann fold, flexible loop deletion, transition state complex, hydrolase
• Biological source: Trypanosoma vivax; More
• Total number of polymer chains: 2
• Total formula weight: 73290.50

Authors

Vandemeulebroucke, A.,De Vos, S.,Van Holsbeke, E.,Steyaert, J.,Versees, W. (deposition date: 2007-11-05, release date: 2008-04-22, Last modification date: 2023-09-20)

Primary citation

Vandemeulebroucke, A.,De Vos, S.,Van Holsbeke, E.,Steyaert, J.,Versees, W.
A Flexible Loop as a Functional Element in the Catalytic Mechanism of Nucleoside Hydrolase from Trypanosoma vivax.
J.Biol.Chem., 283:22272-22282, 2008

PubMed Abstract: The nucleoside hydrolase of Trypanosoma vivax hydrolyzes the N-glycosidic bond of purine nucleosides. Structural and kinetic studies on this enzyme have suggested a catalytic role for a flexible loop in the vicinity of the active sites. Here we present the analysis of the role of this flexible loop via the combination of a proline scan of the loop, loop deletion mutagenesis, steady state and pre-steady state analysis, and x-ray crystallography. Our analysis reveals that this loop has an important role in leaving group activation and product release. The catalytic role involves the entire loop and could only be perturbed by deletion of the entire loop and not by single site mutagenesis. We present evidence that the loop closes over the active site during catalysis, thereby ordering a water channel that is involved in leaving group activation. Once chemistry has taken place, the loop dynamics determine the rate of product release.

PubMed: 18519562
DOI: 10.1074/jbc.M803705200

Experimental method

X-RAY DIFFRACTION (1.4 Å)