Electrostatic effects play a central role in cold adaptation of trypsin

FEBS Letters

Smalås, Arne O.¹  Åqvist, Johan²  Brandsdal, Bjørn Olav¹ 

[1]Department of Chemistry, Faculty of Science, University of Tromsø, N-9037 Tromsø, Norway

[2]Department of Cell and Molecular Biology, Uppsala University, Biomedical Centre, P.O. Box 596, S-75124 Uppsala, Sweden

关键词: Trypsin;    Electrostatics;    Binding affinity;    Molecular dynamics simulation;    Cold adaptation;    Psychrophilic enzyme;   

DOI  :  10.1016/S0014-5793(01)02552-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Organisms that live in constantly cold environments have to adapt their metabolism to low temperatures, but mechanisms of enzymatic adaptation to cold environments are not fully understood. Cold active trypsin catalyses reactions more efficiently and binds ligands more strongly in comparison to warm active trypsin. We have addressed this issue by means of comparative free energy calculations studying the binding of positively charged ligands to two trypsin homologues. Stronger inhibition of the cold active trypsin by benzamidine and positively charged P1-variants of BPTI is caused by rather subtle electrostatic effects. The different affinity of benzamidine originates solely from long range interactions, while the increased binding of P1–Lys and –Arg variants of BPTI is attributed to both long and short range effects that are enhanced in the cold active trypsin compared to the warm active counterpart. Electrostatic interactions thus provide an efficient strategy for cold adaptation of trypsin.

【 授权许可】

Unknown