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

Heme

Red is Heme , gray is α chain and blue is β chain. PDB ID: 1HGA

α1

β1

β2

α2

Amino acid sequence Alignment Glu6

His58

Val62 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 R form

. Hem

. His

. Phe

. val

PDB ID: 1HGA 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(alpha-oxy)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/