1ZN7: Human Adenine Phosphoribosyltransferase Complexed With Prpp, Ade And R5p

Adenine phosphoribosyltransferase (APRT) is an important enzyme component of the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida are unable to synthesize purines de novo and use the salvage pathway for the synthesis of purine bases rendering this biosynthetic pathway an attractive target for antiparasitic drug design. The recombinant human adenine phosphoribosyltransferase (hAPRT) structure was resolved in the presence of AMP in the active site to 1.76 A resolution and with the substrates PRPP and adenine simultaneously bound to the catalytic site to 1.83 A resolution. An additional structure was solved containing one subunit of the dimer in the apo-form to 2.10 A resolution. Comparisons of these three hAPRT structures with other 'type I' PRTases revealed several important features of this class of enzymes. Our data indicate that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and PRPP. Comparative analyses presented here provide structural evidence to propose the role of Glu104 as the residue that abstracts the proton of adenine N9 atom before its nucleophilic attack on the PRPP anomeric carbon. This work leads to new insights to the understanding of the APRT catalytic mechanism.
PDB ID: 1ZN7Download
MMDB ID: 38507
PDB Deposition Date: 2005/5/11
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.83  Å
Source Organism:
Similar Structures:
Biological Unit for 1ZN7: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1ZN7
Label Count Molecule
Proteins (2 molecules)
Adenine Phosphoribosyltransferase(Gene symbol: APRT)
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB