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Structure-Function relationship

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

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Structure-Function relationship

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  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 a2b2: -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. His146) → Asp94-His146 salt bridge → lower O2affinity • Oxy form is a stronger acid (less H+ affinity) than de-oxy (higher H+ affinity) • CO2 (tissues vs. lungs) → H2CO3→ HCO-3+H+→ ↓ pH (less O2affinity) • O2 binding affinity, CO2 & H+ in myoglobin

  6. Conformational Changes Accompany Hb Function • 2,3 BPG have an allosteric binding, lower affinity • Hb F has a higher affinity for O2 due to: • α2γ2 • Less affinity to BPG (adult hemoglobin, βHis143-BPG salt bridge, fetal hemoglobin, the γ –Ser instead of His)

  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; X1—X2(Pro, ProOH)—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 • 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 • Cross-linked intra- & inter-molecularly • Cross-linking amounts varies according to tissue & increases with age • Deficiency of cross-linking (Scurvy & osteogenesis imperfecta)

  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

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