Chapter 5 Protein Function Copyright © 2011 by John Wiley & Sons, Inc. Charlotte W. Pratt | Kathleen Cornely Essential Biochemistry Second Edition

N-terminus C-terminus

F8 His

Y = Fractional Saturation (Y=1 for 100% saturation) p 50 = 2.8 torr

Mb α β

Amino Acid Sequences of Mb and Hb Residues identical in α and β subunits Residues identicl in all 3 Residues invariant in all vertebrates

Globin evolution

Mb Hb p 50 Hb = 26 torr p 50 Mb = 2.8 torr

Hb confomation changes upon oxygenation/deoxygenation

Figure 7-5

DeoxyHb OxyHb

Figure 10-16Triggering mechanism for the T  R transition in Hb. Page 333

Subunit interactions change deoxygenation (b) deoxygenation oxygenation

Figure 10-17The  1 C–  2 FG interface of Hb in (a) the T state and (b) the R state. Page 334

Figure 10-18The hemoglobin  1  2 interface as viewed perpendicularly to Fig Page 335

Box 7-3

Figure 7-15

Figure 7-16

Table 7-1

A map indicating the regions of the world where malaria caused by P. falciparum was prevalent before Page 184

Linus Pauling noted that sHb had a different charge than normal Hb. Single point mutation at position A3 in the β subunit: Glu →Val!!!

Figure 7-19

SHb polymers

Figure 7-18b

Tissue Lungs

Figure 10-7Comparison of the O 2 - dissociation curves of “stripped” Hb and whole blood in 0.01M NaCl at pH 7.0. Page 326

Binding and Release of: O 2, BPG, CO 2, H + 4O 2 + Hb-BPG-CO 2 -H + Hb-(O 2 ) 4 + BPG + CO 2 +H + BPG + CO 2 +H + + Hb-(O 2 ) 4 Hb-BPG-CO 2 -H + + 4O 2 Lungs: Capillaries: Respiring cells: O 2 +MbMb-O 2 Mitochondrion(O 2 ) + Mb CO 2

Binding of BPG to deoxyHb.

The effects of BPG and CO 2, both separately and combined, on hemoglobin’s O 2 -dissociation curve compared with that of whole blood (red curve).

Fibrous proteins Actin and Tubulin

Actin monomer ATP ATP is hydrolyzed to ADP to drive the polymerization reaction

F-actin (not G-actin catalyze ATP hydrolysis

Polymerization is reversible

Microfilaments help cells move

β-Tubulin Tubulin αβ dimer with bound G

Assembly of a microtubule

Tubulin depolymerization Protofilaments curve away from the microtubule and separate before dimers dissociate

Microtubules in a dividing cell!

Product of the meadow saffron plant causes microtubules to depolymerize and therefore blocks cell division!

Originally from the endangered Pacific yew tree Binds β tubulin in a microtubule but not to free tubulin preventing depolymerization and thus cell division. Toxic to rapidly dividing cells.

SEM of Human skin!!!

Keratin forms a coil-coil structure.

HAIR

Collagen

Collagen: mostly (Gly-Pro-Hyp) n

Narrow lh helix Pro Hyp Gly

Collagen triple helix

Cross-linking of collagen fibers Cross-linking increases with age—skin is less plastic

A CHILD with a collagen defect Osteogenisis imperfecta

Myosin

Thick filaments of Myosin