PDBsum entry 1qcc

Transferase

PDB id: 1qcc

Contents

Protein chain

236 a.a. *

Ligands

CIT

Waters ×215

* Residue conservation analysis

PDB id:

1qcc

Name:

Transferase

Title:

Crystal structures of adenine phosphoribosyltransferase from leishmania donovani

Structure:

Adenine phosphoribosyltransferase. Chain: a. Synonym: aprt. Engineered: yes

Source:

Leishmania donovani. Organism_taxid: 5661. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.98Å R-factor: 0.187 R-free: 0.241

Authors:

C.L.Phillips,B.Ullman,R.G.Brennan,C.P.Hill

Key ref:

C.L.Phillips et al. (1999). Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani. EMBO J, 18, 3533-3545. PubMed id: 10393170 DOI: 10.1093/emboj/18.13.3533

Date:

01-May-99 Release date: 21-Jul-99

Protein chain

Q27679  (Q27679_LEIDO) -  adenine phosphoribosyltransferase from Leishmania donovani

Seq: 237 a.a.

Struc: 236 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.2.7 - adenine phosphoribosyltransferase.
• Pathway: Ribose activation
• Reaction: AMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + adenine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1093/emboj/18.13.3533

EMBO J 18:3533-3545 (1999)

PubMed id: 10393170

Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani.

C.L.Phillips, B.Ullman, R.G.Brennan, C.P.Hill.

ABSTRACT

The enzyme adenine phosphoribosyltransferase (APRT) functions to salvage adenine by converting it to adenosine-5-monophosphate (AMP). APRT deficiency in humans is a well characterized inborn error of metabolism, and APRT may contribute to the indispensable nutritional role of purine salvage in protozoan parasites, all of which lack de novo purine biosynthesis. We determined crystal structures for APRT from Leishmania donovani in complex with the substrate adenine, the product AMP, and sulfate and citrate ions that appear to mimic the binding of phosphate moieties. Overall, these structures are very similar to each other, although the adenine and AMP complexes show different patterns of hydrogen-bonding to the base, and the active site pocket opens slightly to accommodate the larger AMP ligand. Whereas AMP adopts a single conformation, adenine binds in two mutually exclusive orientations: one orientation providing adenine-specific hydrogen bonds and the other apparently positioning adenine for the enzymatic reaction. The core of APRT is similar to that of other phosphoribosyltransferases, although the adenine-binding domain is quite different. A C-terminal extension, unique to Leishmania APRTs, extends an extensive dimer interface by wrapping around the partner molecule. The active site involves residues from both subunits of the dimer, indicating that dimerization is essential for catalysis.

Selected figure(s)

Figure 7.
Figure 7 Schematic representation of contacts to AMP. Hydrogen bonds and metal–ligand contacts are indicated with a dotted line and defined as for Figure 8.

Figure 10.
Figure 10 Superposition of APRT active site structures. AMP–APRT red; apo-AS–APRT green; Ade–APRT A orientation light blue; Ade–APRT B orientation dark blue.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 3533-3545) copyright 1999.

Figures were selected by an automated process.