2F67

Crystal structure of Nucleoside 2-deoxyribosyltransferase from Trypanosoma brucei at 1.6 A resolution with BENZO[CD]INDOL-2(1H)-ONE bound

Summary for 2F67

• Entry DOI: 10.2210/pdb2f67/pdb
• Related: 2A0K 2F2T 2F62 2F64
• Descriptor: Nucleoside 2-deoxyribosyltransferase, SULFATE ION, BENZO[CD]INDOL-2(1H)-ONE, ... (5 entities in total)
• Functional Keywords: sgpp, structural genomics, psi, protein structure initiative ndrt, nucleoside 2-deoxyribosyltransferase, trypanosoma brucei, structural genomics of pathogenic protozoa consortium, transferase
• Biological source: Trypanosoma brucei
• Total number of polymer chains: 2
• Total formula weight: 38138.87

Authors

Bosch, J.,Robien, M.A.,Hol, W.G.J.,Structural Genomics of Pathogenic Protozoa Consortium (SGPP) (deposition date: 2005-11-28, release date: 2005-12-06, Last modification date: 2024-10-09)

Primary citation

Bosch, J.,Robien, M.A.,Mehlin, C.,Boni, E.,Riechers, A.,Buckner, F.S.,Van Voorhis, W.C.,Myler, P.J.,Worthey, E.A.,DeTitta, G.,Luft, J.R.,Lauricella, A.,Gulde, S.,Anderson, L.A.,Kalyuzhniy, O.,Neely, H.M.,Ross, J.,Earnest, T.N.,Soltis, M.,Schoenfeld, L.,Zucker, F.,Merritt, E.A.,Fan, E.,Verlinde, C.L.,Hol, W.G.J.
Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma brucei nucleoside 2-deoxyribosyltransferase.
J.Med.Chem., 49:5939-5946, 2006

PubMed Abstract: The 1.8 A resolution de novo structure of nucleoside 2-deoxyribosyltransferase (EC 2.4.2.6) from Trypanosoma brucei (TbNDRT) has been determined by SADa phasing in an unliganded state and several ligand-bound states. This enzyme is important in the salvage pathway of nucleoside recycling. To identify novel lead compounds, we exploited "fragment cocktail soaks". Out of 304 compounds tried in 31 cocktails, four compounds could be identified crystallographically in the active site. In addition, we demonstrated that very short soaks of approximately 10 s are sufficient even for rather hydrophobic ligands to bind in the active site groove, which is promising for the application of similar soaking experiments to less robust crystals of other proteins.

PubMed: 17004709
DOI: 10.1021/jm060429m

Experimental method

X-RAY DIFFRACTION (1.6 Å)