Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online





Learning Goals/Objectives for Chapter 5C:  After class and this reading, students will be able to

  • explain the similarities and differences in structure between myoglobin and hemoglobin in the deoxy and oxy states
  • state structural features of Hb that stabilizes the deoxystate and the oxystate
  • draw graphs of fractional saturation Y vs L (or pO2) for Mb and Hb  (at different pHs and in the presence of CO2 for Hb) and explain their apparent similarities and differences
  • draw a thermodynamic cycle for the interactions of O2, CO2 and H+ with deoxy-Hb and oxy-Hb
  • explain how Hill Plot analysis can account for cooperative binding curves for Hb.
  • give a simple explanation of the MWC model and draw cartoon representations of Hb in the T and R state, describing the characteristics of those states
  • given definitions of the MWC parameters (L, KT, KR, c, and α) and the assumptions of the model, explain how this model accounts for cooperative sigmoidal binding curves for Hb and dioxygen.
  • draw cartoon models and explain differences in lock and key, induced fit, and conformational selection as mechanisms for ligand bind.
  • Explain biological advantages elicited on ligand binding by intrinsically disordered proteins

C1.  Myoglobin, Hemoglobin, and their Ligands

Almost all biochemistry textbooks start their description of the biological functions of proteins using the myoglobin and hemoglobin as exemplars.  These are very rational approaches since they have become model systems to describe the binding of simple ligands,  like dioxygen (O2), CO2, and H+,  and how the structure of the protein determines and is influenced by binding of ligands. 

Yet in a way these "ligands" are dissimilar to perhaps the majority of other proteins which bind small  ligands such as substrates (for enzymes), inhibitors and activators or large "ligands" such as other proteins, nucleic acids, carbohydrates and lipids. These type of ligands are reversibly bound through classical intermolecular forces (IMFs), such as hydrogen bonds, London dispersion forces, dipole-dipole interactions, and ion-ion interactions.  In addition to these are the less commonly discussed pi-pi (aromatic) interactions and cation-pi (aromatic) interactions.

YouTube: Less Common Discussed IMFs -  pi-pi, cation-pi interactions, and halogen bnding

The classic ligands that reversibly bind to hemoglobin,  dioxygen, carbon dioxide, and protons, are bound covalently.  Dioxygen binds to a heme Fe2+, protons obviously bind to proton acceptors (like His), while CO2 binds covalently as if forms a carbamate with the N terminus of one of the hemoglobin chains.

This discrepancy in ligand binding mode can be explained easily for dioxygen as it forms a coordinate or dative covalent bond with the transition metal ion Fe+2.  In ordinary covalent bonds, each bonded atom contributes to and shares the two electron in the bond.  In coordinate or dative covalent bonds, the ligand, a Lewis base, contributes both electrons in the bond.  Both electrons are still considered to be "owned" by the ligand and not by the transition metal ion, a Lewis acid.  Hence the ligand can readily dissociate from the metal ion, much as a ligand bound through classical IMFs can.  This analogy can be extended to protons which are also Lewis acids (with no contributing electrons) as they react with Lewis bases (lone pair donors) on atoms such as N on a His side chain.  

Mb (a monomer containing 8 α−helices, A-H) and Hb (a heterotetramer with two α -and two β−subunits, each which also contains 8 α−helices) are both oxygen binding proteins. Dioxygen is transported from lungs, gills, or skin of an animal to capillaries, where it can be delivered to respiring tissue.  It has a low solubility in blood (0.1 mM).  Whole blood, which contains 150 g Hb/L, can carry up to 10 mM dioxygen.  Invertebrate can have alternative proteins for oxygen binding, including hemocyanin, which contains Cu and hemerythrin, a non-heme protein.  On binding dioxygen, solutions of Hb change color to bright red.  Solutions of hemocyanin and hemerythrin change to blue and burgundy colored, respectively, on binding dioxygen. Some Antarctic fish don't require Hb since dioxygen is more soluble at low temperature.  Mb is found in the muscle, and serves as a storage protein for oxygen transported by Hb.  Some information about the proteins is given below:


Heme group:

Figure:  Heme

Figure:  Heme-O2 Octahedral Complex

  Jmol:   Updated  deoxy-heme and carbon monoxide-heme Jmol14 (Java) |  JSMol  (HTML5)


Jmol:   Updated  Met-Myoglobin Jmol14 (Java) |  JSMol  (HTML5)

Difference between Hb and Mb

Jmol:   Hemoglobin 


Return to Chapter 5C:  Model Binding Sections

Return to Biochemistry Online Table of Contents

 Archived version of full Chapter 5C:  Model Binding Systems


Creative Commons License
Biochemistry Online by Henry Jakubowski is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.