1. Structure-Function relationship Nafith Abu Tarboush DDS, MSc, PhD natarboush@ju.edu.jo www.facebook.com/natarboush

2. The heme

3. Myoglobin The first to be determined structurally A single polypeptide chain (153 a.a) A single heme in a hydrophobic pocket 8  -helices; no  -sheets Most polar (exterior) Nonpolar (interior) Two His residues Fe(II) coordination

4. Hemoglobin A tetramer  2  2:  -chains (141 a.a) &  -chains (146 a.a) 1 heme group in each (4O2) Myoglobin (storage) vs. hemoglobin (transport): positive cooperativity & saturation percentage lungs (100 torr), capillaries (20 torr)

5. Conformational Changes Accompany Hb Function Oxygenated vs. deoxygenated (different crystal structures) Bohr effect: (tissues vs. lungs): lower pH → ↑H + → protonation (ex. His 146 ) → Asp 94 - His 146 salt bridge → lower O 2 affinity Oxy form is a stronger acid (less H + affinity) than de-oxy (higher H + affinity) CO 2 (tissues vs. lungs) → H 2 CO 3 → HCO - 3 +H + → ↓ pH (less O 2 affinity) O 2 binding affinity, CO 2 & H + in myoglobin

6. 2,3 BPG have an allosteric binding, lower affinity Hb F has a higher affinity for O 2 due to: α2γ2 Less affinity to BPG (adult hemoglobin, βHis143-BPG salt bridge, fetal hemoglobin, the γ –Ser instead of His) Conformational Changes Accompany Hb Function

7. The Collagen Triple Helix The most abundant protein in vertebrates Organized in water-insoluble fibers Have a great strength Consists of three polypeptide chains wrapped around each other in a ropelike twist, or triple helix Has a repeating sequence of the amino acids; X 1 —X 2 (Pro, Pro OH )—Gly Hydroxy-lysine also occurs in collagen The triple helix (tropocollagen) is 300 nm long and 1.5 nm in diameter Held together by H-bonding Each strand have ≈800 amino acids (300KDa)

8. Collagen, types & diseases Cross-linked intra- & inter-molecularly Cross-linking amounts varies according to tissue & increases with age Deficiency of cross-linking (Scurvy & osteogenesis imperfecta) Collagen I: skin, tendon, vessels, bone Collagen II: cartilage Collagen III: reticular fibers, alongside type I Collagen IV: basement membrane Collagen V: cell surfaces, hair and placenta

9. Keratin Principal component of epidermis and related appendages (hair, horn, nails, & feathers) α(mammals) or β(birds & reptiles) Mammals: ≈30 types, tissue-specific Structure: α-helix, coiled coil Classified as “hard” or “soft” according to S content (Cys)

10. Elastin Rich in hydrophobic amino acids (ex. Gly, Val & Pro); mobile hydrophobic regions bonded by crosslinks between Lys Elastic fibers in arteries are composed mainly of elastin (≈70%) Tropoelastin → Elastin (Lysyl oxidase)

11. Elastin & hydroxylysine Collagen contain lysine that can be hydroxylated by lysyl-hydroxylase to form hydroxyl-lysine or by lysyl-oxidase to form Allysine Cross-linking of elastin occurs through the enzyme lysyl-oxidase producing the Allysine, the pathway for oxidation through lysyl- hydroxylase does not occur in elastin