1TC1

A 1.4 ANGSTROM CRYSTAL STRUCTURE FOR THE HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE OF TRYPANOSOMA CRUZI

Summary for 1TC1

• Entry DOI: 10.2210/pdb1tc1/pdb
• Descriptor: PROTEIN (HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE), FORMYCIN B, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: transferase, phosphoribosyltransferase, purine salvage, nucleotide metabolism
• Biological source: Trypanosoma cruzi
• Cellular location: Cytoplasm : Q27796
• Total number of polymer chains: 2
• Total formula weight: 51855.34

Authors

Focia, P.J.,Craig III, S.P.,Nieves-Alicea, R.,Fletterick, R.J.,Eakin, A.E. (deposition date: 1998-09-30, release date: 1999-10-07, Last modification date: 2023-08-23)

Primary citation

Focia, P.J.,Craig III, S.P.,Nieves-Alicea, R.,Fletterick, R.J.,Eakin, A.E.
A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi.
Biochemistry, 37:15066-15075, 1998

PubMed Abstract: The hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi, etiologic agent of Chagas' disease, was cocrystallized with the inosine analogue Formycin B (FmB) and the structure determined to 1.4 A resolution. This is the highest resolution structure yet reported for a phosphoribosyltransferase (PRT), and the asymmetric unit of the crystal contains a dimer of closely associated, nearly identical subunits. A conserved nonproline cis peptide in one active-site loop exposes the main-chain nitrogen to the enzyme active site, while the adjacent lysine side chain interacts with the other subunit of the dimer, thereby providing a possible mechanism for communication between the subunits and their active sites. The three-dimensional coordinates for the invariant Ser103-Tyr104 dipeptide are reported here for the first time. These are the only highly conserved residues in a second active-site loop, termed the long flexible loop, which is predicted to close over the active site of HPRTs to protect a labile transition state [Eads et al. (1994) Cell 78, 325-334]. This structure represents a major step forward in efforts to design/discover potent selective inhibitors of the HPRT of T. cruzi.

PubMed: 9790669
DOI: 10.1021/bi981052s

Experimental method

X-RAY DIFFRACTION (1.41 Å)