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PROTEIN PHYSICS LECTURE 25

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 E i = ( k i /2 )( x i ) 2 = F 2 / ( 2k i )

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PROTEIN PHYSICS LECTURE 25

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  1. PROTEIN PHYSICS LECTURE 25 PROTEINS AT ACTION

  2. Preferential binding of TS: RIGID enzyme

  3. Preferential binding of TS: RIGID enzyme F = k1x1= - k2x2 Ei = (ki/2)(xi)2 = F2/(2ki) Hooke’s & 2-nd Newton’s Energy is concentrated laws 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 ~ D3 – mass;  – viscosity tkinet 10-13 sec  (D/nm)2in water

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

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

  6. Similar folds with different active sites: different biochemical function

  7. Standard positions of active sites in protein folds

  8. MOTIONS

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

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

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

  12. Movement in quaternary structure: Hemoglobin vs. myoglobin

  13. Myosin Actin Mechanochemical cycle

  14. SUMMARY

  15. PROTEIN PHYSICS • Interactions • Structures • Selection • States & transitions

  16. Intermediates & nuclei • Structure prediction & bioinformatics • Protein engineering & design • Functioning

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