Hemoglobin Hb Arwa Almejbel Introduction • First studied in the 1800th. • Third of red blood cells is hemoglobin. • Found in bacteria ,eukaryotic organisms and archea. • The heme part is synthesized in mitochondria and cytosol in While the globin protein parts are synthesized by ribosomes in the cytosol. • Function: to transport the oxygen and maintain the round shape of the RBCs. Hemoglobin A Structure α1 β2 Heme β1 α2 Red is Heme , gray is α chain and blue is β chain. PDB ID: 1HGA Amino acid sequence Alignment Glu6 Val62 His58 His87 Key amino acids in Hemoglobin PDB ID: 1HGA Oxygen binding • Cooperative binding • Binding to the 1st O2 facilitates the binding of 2nd ,3rd and 4th O2. • Binding to O2 causes conformational changes. . O2 . PHE . H2O . HIS . VAL PDB ID: 1GZX Oxygen-Hemoglobin binding • • • Partial pressure of oxygen determines how much oxygen binds. The affinity of O2 depends on PH. Small amount of CO reduces Hb ability to transport O2 https://thechronicleflask.wordpress.com/tag/red-blood-cells/ The T and R transition T form PDB ID: 1HGA R form PDB ID: 1BBB Salt Bridges in Deoxy Hb http://employees.csbsju.edu/hjakubowski/classes/ch331/bind/olbindhemoglobin.html Mutations in hemoglobin (hemoglobinopathies): Sickle cell anemia (Hb S): http://www.cc.nih.gov/ccc/ccnews/nov99/ structure PDB ID: 1GZX Hydrophobic pocket PDB ID: 2HBS Val6, Leu88 , Phe85 • Lifetime of RBC in Sickle cell is 20 days. • As the cell sickle it causes a low oxygen conc. region. • Lose of elasticity • Unable to flow through capillaries. References • • • • • • • • • • • Harrington, D.J., Adachi, K., Royer Jr., W.E. (1997) The high resolution crystal structure of deoxyhemoglobin S. J.Mol.Biol. 272: 398-407 Shaanan, B. Structure of human oxyhaemoglobin at 2.1 A resolution. (1983) J.Mol.Biol. (171) 31-59 http://employees.csbsju.edu/hjakubowski/classes/ch331/bind/olbindhemoglobin.html Marengo-Rowe,A. J. (2006) Structure-function relations of human hemoglobins. Proc (Bayl Univ Med Cent)19(3) 239–245. Paoli, M., Liddington, R., Tame, J., Wilkinson, A., Dodson, G. (1996) Crystal structure of T state haemoglobin with oxygen bound at all four haems. J.Mol.Biol. 256(4):775-92. PDB ID: 1BBB Liddington, R., Derewenda, Z., Dodson, E., Hubbard,R, and Dodson, G. (1992) High resolution crystal structures and comparisons of T-state deoxyhaemoglobin and two liganded T-state haemoglobins: T(alphaoxy)haemoglobin and T(met)haemoglobin. J Mol Biol. 228(2)551-79. PDB ID: 1HGA Starr C., Taggart, R. (2001) Biology: The Unity and Diversity of Life (6th Ed.) pp. 183-227, Brooks/Cole, Pacific Grove. Rousseot, N., Jaenicke, E., Lamkemeyer, T., Harris, J.R., Pirow, R. (2006) Native and subunit molecular mass and quarternary structure of the hemoglobin from the primitive branchiopod crustacean Triops cancriformis. FEBS J 17, 4055-71. Campbell, N.A., Reece, J.B., Taylor, M.R., Simon, E.J. (2006) Biology Concepts and Connections (Eds.) (5th Ed.) pp. 46-462, Pearson, San Francisco. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P. (2002) Molecular Biology of the Cell. (Eds.), pp. 461, Garland Science, New York. http://www.cc.nih.gov/ccc/ccnews/nov99/