Müller, Jonathan W.; Link, Nina C; Matena, Anja; Hoppstock, Lukas; Rüppel, Alma; Bayer, Peter; Blankenfeldt, Wulf:

Crystallographic Proof for an Extended Hydrogen Bonding Network in Small Prolyl Isomerases

In: Journal of the American Chemical Society, Jg. 133 (2011) ; Nr. 50, S. 20096 – 20099
Zeitschriftenaufsatz / Fach: Biologie
Fakultät für Biologie » Chemische Biologie
Parvulins compose a family of small peptidylprolyl
isomerases (PPIases) involved in protein folding and
protein quality control. A number of amino acids in the catalytic cavity are highly conserved, but their precise role within the catalytic mechanismis unknown. The 0.8 Å crystal structure of the prolyl isomerase domain of parvulin Par14 shows the electron density of hydrogen atoms between the D74, H42, H123, and T118 side chains. This threonine
residue has previously not been associated with catalysis, but a corresponding T152A mutant of Pin1 shows a dramatic
reduction of catalytic activity without compromising protein
stability. The observed catalytic tetrad is strikingly conserved in Pin1- and parvulin-type proteins and hence constitutes a common feature of small peptidyl prolyl isomerases.