5etj

Crystal structure of purine nucleoside phosphorylase (E258D, L261A) mutant from human complexed with DADMe-ImmG and phosphate

spinqualitylabelsall models 5etj, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5etj is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: IM5, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PNPH_HUMAN Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179. It leads to a severe T-cell immunodeficiency with neurologic disorder in children. Function PNPH_HUMAN The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. Publication Abstract from PubMed The relevance of sub-picosecond protein motions to the catalytic event remains a topic of debate. Heavy enzymes (isotopically substituted) provide an experimental tool for bond-vibrational links to enzyme catalysis. A recent transition path sampling study with heavy purine nucleoside phosphorylase (PNP) characterized the experimentally observed mass-dependent slowing of barrier crossing (Antoniou, D.; Ge, X.; Schramm, V. L.; Schwartz, S. D. J. Phys. Chem. Lett. 2012, 3, 3538). Here we computationally identify second-sphere amino acid residues predicted to influence the freedom of the catalytic site vibrational modes linked to heavy enzyme effects in PNP. We mutated heavy and light PNPs to increase the catalytic site vibrational freedom. Enzymatic barrier-crossing rates were converted from mass-dependent to mass-independent as a result of the mutations. The mutagenic uncoupling of femtosecond motions between catalytic site groups and reactants decreased transition state barrier crossing by 2 orders of magnitude, an indication of the femtosecond dynamic contributions to catalysis. Modulating Enzyme Catalysis through Mutations Designed to Alter Rapid Protein Dynamics.,Zoi I, Suarez J, Antoniou D, Cameron SA, Schramm VL, Schwartz SD J Am Chem Soc. 2016 Mar 16;138(10):3403-9. doi: 10.1021/jacs.5b12551. Epub 2016, Mar 8. PMID:26927977 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Purine nucleoside phosphorylase 3D structures

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