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Erika A. Taylor, Ph.D.

Life Sciences

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Second-Sphere Amino Acids Contribute To Transition-State Structure In Bovine Purine Nucleoside Phosphorylase, Lei Li, Minkui Luo, Mahmoud Ghanem, Erika A. Taylor, Vern L. Schramm Feb 2008

Second-Sphere Amino Acids Contribute To Transition-State Structure In Bovine Purine Nucleoside Phosphorylase, Lei Li, Minkui Luo, Mahmoud Ghanem, Erika A. Taylor, Vern L. Schramm

Erika A. Taylor, Ph.D.

Transition-state structures of human and bovine of purine nucleoside phosphorylases differ, despite 87% homologous amino acid sequences. Human PNP (HsPNP) has a fully dissociated transition state, while that for bovine PNP (BtPNP) has early SN1 character. Crystal structures and sequence alignment indicate that the active sites of these enzymes are the same within crystallographic analysis, but residues in the second-sphere from the active sites differ significantly. Residues in BtPNP have been mutated toward HsPNP, resulting in double (Asn123Lys; Arg210Gln) and triple mutant PNPs (Val39Thr; Asn123Lys; Arg210Gln). Steady-state kinetic studies indicated unchanged catalytic activity, while pre-steady-state studies indicate that the chemical ...