Biochemarizonaeduclassesbioc462462ajmolmyoglob

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Unformatted text preview: y metabolism –  intracellular O2 transport Mb and Hb are similar in many ways: -polypeptide sequence is somewhat similar -each polypeptide has a heme that binds 1 O2 molecule -overall structures of subunits are similar Myoglobin (Mb) monomeric single polypeptide chain, 153 residues Hemoglobin (Hb) heterotetrameric (α2β2) 2 α chains 141 residues each 2 β chains 146 residues each Sequence alignment of Mb, Hbα, and Hbβ The three chains are homologous repeated duplication and divergence from a common ancestor Myoglobin: first globular protein structure, 1957-58 Kendrew (shared Nobel Prize w/Perutz) Tertiary Structure of Myoglobin •  Jmol structure of oxymyoglobin: http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/myoglob/ myoglob.html loop CD •  “globin fold”: 8 α helices (A-H) Connections AB, BC, etc. helix B •  In Mb and Hb, residues are numbered within helices –  Permits comparison of sequences and functional residues among different globin chains –  e.g., “proximal His” (helps bind heme in protein) •  residue 93 in Mb •  residue 87 in Hb α •  residue 92 in Hb β •  8th residue in helix F in all 3 chains (residue F8) Mb structure, continued •  interior densely packed with buried hydrophobic residues •  polar R groups are mostly at outer surface, hydrated –  2 exceptions: His F8 and His E7, which bind the heme •  Most of the helices are amphipathic Lehninger Principles, Fig. 4-16 (blue residues: Leu, Ile, Val, Phe; red is heme) Heme: iron protoporphyrin IX, with bound Fe2+ HEME: Prosthetic group: metal ion or organic or metallo-organic compound other than an amino acid that’s tightly bound to a protein (binding covalent or tight non-covalent), required for the protein’s function/activity holoprotein <==> apoprotein + prosthetic group Berg, Tymoczko & Stryer, Biochemistry, 6th ed., p.184 6 coordination positions of heme Lehninger Principles, Fig. 5-1 Free heme has two open coordination sites The protein provides a ligand (the proximal histidine) The other open site binds to O2 When O2 is bound to Mb or Hb, Fe is in the porphyrin plane; when O2 not bound, the Fe is displaced out of the plane Proximal His (His F8) coordinated to Heme Fe2+ Lehninger Principles, Fig. 5-2 Heme binds O2. What’s the function of the protein? Heme is sequestered deep within the protein, so access to it is restricted Restriction prevents two hemes interacting with one O2, which would result in the oxidation of Fe2+ to Fe3+ (metMb or metHb) Heme binds O2. What’s the function of the protein? Protein regulates access to the heme Free heme binds CO 20,000X better than O2 Preferred binding geometries of O2 and CO Heme binds O2. What’s the function of the protein? Protein regulates access to the heme distal histidine distal histidine O C in the protein Heme in Mb binds CO only 200X better, since distal His (E7) prevents linear binding of CO Myoglobin binds single O2 molecule •  [Ligand] = [O2] •  O2 concentra=on in gas pressure units (kPa) = pO2 •  Kd in pressure units = P50 partial pressure = O2 concentra=on (pO2) not –log that gives θ = 0.5 = ~ 0.26 kPa (Lehninger Principles Fig. 5-4b) Myoglobin is an oxygen storage protein in tissues What does this hyperbolic binding curve reflect? How is it related to the function of myoglobin?...
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This test prep was uploaded on 02/25/2014 for the course BIOC 462A taught by Professor Ziegler,baldwin during the Spring '08 term at University of Arizona- Tucson.

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