PROTEIN PHYSICS LECTURE 25 PROTEINS AT ACTION Preferential

PROTEIN PHYSICS LECTURE 25 PROTEINS AT ACTION

Preferential binding of TS: RIGID enzyme

Preferential binding of TS: RIGID enzyme F = k 1 x 1 = - k 2 x 2 Hooke’s & 2 -nd Newton’s laws Ei = (ki /2)(xi)2 = F 2/(2 ki ) Energy is concentrated in the softer body. Effective catalysis: when substrate is softer than protein Kinetic energy cannot be stored for catalysis Friction stops a molecule within picoseconds: m(dv/dt) = -(3 D )v [Stokes law] D – diameter; m ~ D 3 – mass; – viscosity tkinet 10 -13 sec (D/nm)2 in water

Catalysis: stabilization of the transition state Theory: Pauling & Holden Experimental verification: Fersht _____ P ______

Different folds with the same active site: the same biochemical function

Similar folds with different active sites: different biochemical function

Standard positions of active sites in protein folds

MOTIONS

Double sieve: movement of substrate from one active site to another

Movement in two-domain enzyme: One conformation for binding (and release), another for catalysis

Two-domain dehydrogenases: Universal NAD-binding domain; Individual substrate-binding domain

Movement in quaternary structure: Hemoglobin vs. myoglobin

Myosin Actin Mechanochemical cycle

SUMMARY

PROTEIN PHYSICS · Interactions · Structures · Selection · States & transitions

· Intermediates & nuclei · Structure prediction & bioinformatics · Protein engineering & design · Functioning