2MAS

PURINE NUCLEOSIDE HYDROLASE WITH A TRANSITION STATE INHIBITOR

Summary for 2MAS

• Entry DOI: 10.2210/pdb2mas/pdb
• Descriptor: INOSINE-URIDINE NUCLEOSIDE N-RIBOHYDROLASE, CALCIUM ION, 2-(4-AMINO-PHENYL)-5-HYDROXYMETHYL-PYRROLIDINE-3,4-DIOL, ... (4 entities in total)
• Functional Keywords: purine nucleoside hydrolase, inosine, uridine, iu-nh, hydrolase, purine nucleosidase
• Biological source: Crithidia fasciculata
• Total number of polymer chains: 4
• Total formula weight: 137883.26

Authors

Degano, M.,Schramm, V.L.,Sacchettini, J.C. (deposition date: 1996-10-17, release date: 1997-08-12, Last modification date: 2024-05-22)

Primary citation

Degano, M.,Almo, S.C.,Sacchettini, J.C.,Schramm, V.L.
Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor.
Biochemistry, 37:6277-6285, 1998

PubMed Abstract: Nucleoside N-ribohydrolases are targets for disruption of purine salvage in the protozoan parasites. The structure of a trypanosomal N-ribohydrolase in complex with a transition-state inhibitor is reported at 2.3 A resolution. The nonspecific nucleoside hydrolase from Crithidia fasciculata cocrystallized with p-aminophenyliminoribitol reveals tightly bound Ca2+ as a catalytic site ligand. The complex with the transition-state inhibitor is characterized by (1) large protein conformational changes to create a hydrophobic leaving group site (2) C3'-exo geometry for the inhibitor, typical of a ribooxocarbenium ion (3) stabilization of the ribooxocarbenium analogue between the neighboring group 5'-hydroxyl and bidentate hydrogen bonds to Asn168; and (4) octacoordinate Ca2+ orients a catalytic site water and is liganded to two hydroxyls of the inhibitor. The mechanism is ribooxocarbenium stabilization with weak leaving group activation and is a departure from glucohydrolases which use paired carboxylates to achieve the transition state.

PubMed: 9572842
DOI: 10.1021/bi973012e

Experimental method

X-RAY DIFFRACTION (2.3 Å)