Chapter 5 Chem 341 Suroviec Fall 2013

I. Introduction Every protein has a unique 3-D structure

II. Myoglobin Small intercellular protein

A. Heme group Heme contains 4 pyrrole groups Fe(II) atom at the center is coordinated by the 4 porphyrin N atoms and one N from a His side chain

B. Equilibrium of O 2 binding Myoglobin binding of O 2 is simple equilibrium

C. Binding Curve Steepness of hyperbola increases as K decreases

III. Hemoglobin Structure & Mechanism 4 polypeptide chains –2  subunits –2  subunits

III. Hemoglobin Structure & Mechanism Oxygenation causes extensive quaternary structural changes Oxy- and Deoxy- Hb have different forms

A. Binding of O 2 T-state (deoxy) R-state (oxy) In T state (blue) Fe(II) located 0.6 Å out of heme plane When O 2 binds Fe-N porphyrin bonds contract and Fe(II) moves in plane (red)

B. 2 Stable Positions Difference between T and R occur at  1 -  2 and  2 -  1 interface

C. Role of Globin in Binding of O 2 Protect Fe(II) His attached to backside of porphyrin

D. Relative Stability of T and R With no O 2 present: T more stable With O 2 present: R more stable

V. Hemoglobin binding and pH Effect of pH on Hb transport Lung pH = 7.6 Blood pH = 7.2 pO 2 in tissues = 30 torr pO 2 in lungs = 95 torr

Bohr Effect

VI. 2 – 3 Bis-phosphoglycerate Red blood cells use BPG to fine tune hemoglobin function

VII. Abnormal Hemoglobins Sickle Cell Anemia –Deoxyhemoglobin S forms insoluble filaments that deform red blood cells –Rigid sickle shaped cells cannot pass through the capillaries –Results in tissue death: lack of oxygen –Mutant hemoglobin where hemoglobin S contains Val instead of Glu at the 6th position of the  chain –Causes polymerization of hemoglobins

VIII. Structural Proteins Typical eukaryotic cells have 3 types of cytoskeletal proteins that form fibers

A. Microfilaments Made of actin Network of microfilaments support plasma membrane

B. Microfilaments extend/retract Polymerization of actin monomers is reversible process so the polymer undergoes constant shrinking and growing as subunits add to and dissociate from one or both ends of the microfilaments

C. Microtubules Microtubules are cytoskeletal fibers built from globular protein subunits Microtubules can assemble and disassemble on a time scale that allow the cell to rapidly change shape in response to external or internal stimuli

D.  -Keratin Intermediate filaments are structural proteins Chemically un-reactive Component of hair, horns, nails and feathers  -helix shape, but exhibits smaller than expected spacing - due to coiled coil structure

E. Collagen Most abundant animal protein Major stress-bearing components of connective tissues (bone, teeth, tendons) Has distinct amino acid composition –Every 3 rd amino acid = glycine

E. Collagen Cross-linking between fibrils also increases insolubility Can’t be S-S bonds Cross-link between Lys and His chains using Lysyl oxidase Tends to occur near termini