4ECE: Crystal Structure Of Purine Nucleoside Phosphorylase (w16y, W94y, W178y, H257w) Mutant From Human Complexed With Guanine

Purine nucleoside phosphorylase (PNP) is a target for leukemia, gout, and autoimmune disorders. Dynamic motion of catalytic site loops has been implicated in catalysis, but experimental evidence was lacking. We replaced catalytic site groups His257 or His64 with 6-fluoro-tryptophan (6FW) as site-specific NMR probes. Conformational adjustments in the 6FW-His257-helical and His64-6FW-loop regions were characterized in PNP phosphate-bound enzyme and in complexes with catalytic site ligands, including transition state analogs. Chemical shift and line-shape changes associated with these complexes revealed dynamic coexistence of several conformational states in these regions in phosphate-bound enzyme and altered or single conformations in other complexes. These conformations were also characterized by X-ray crystallography. Specific (19)F-Trp labels and X-ray crystallography provide multidimensional characterization of conformational states for free, catalytic, and inhibited complexes of human PNP.
PDB ID: 4ECEDownload
MMDB ID: 107299
PDB Deposition Date: 2012/3/26
Updated in MMDB: 2013/03
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 4ECE: trimeric; determined by author and by software (PISA)
Molecular Components in 4ECE
Label Count Molecule
Proteins (3 molecules)
Purine Nucleoside Phosphorylase(Gene symbol: PNP)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB