Lectures 8 & 9 Flashcards
What is hemoglobin?
the red protein that is found in red blood cells
What is hemoglobin involved in?
oxygen transport (and carbon dioxide)
Hemoglobin makes up around __% of the red blood cells’ dry content.
97%
How many heme groups does hemoglobin have, and what can they do?
4 heme groups
-bind 4 oxygen atomes
-they give hemoglobin its red color
What’s the first protein whose 3D structure was determined?
hemoglobin
the beginning of structural biology
Each red blood cell contains about how many hemoglobin molecules?
~ 250,000 hemoglobin molecules
Oxyhemoglobin
oxygen bearing (Fe+2.8) hemoglobin
Deoxyhemoglobin
oxygen free (Fe2+) hemoglobin
How many atoms are bound to iron and in what coordination?
six atoms
octahedral coordination
square pyramid
What does ferrous iron (Fe+2) like to lose, and what to?
likes to lose e- to O2
When oxygen is binding to heme, what must Hb do?
must keep reaction from going to completion
Which is NOT one of the major electrostatic interactions that drive protein folding?
A. hydrophilic interactions
B. hydrogen bond interactions
C. salt bridge interactions
D. van DerWaal’s interactions
A. hydrophilic interactions
What is the Mb O2 binding curve?
hyperbolic, indicates a single Kd (affinity)
What is the Hb O2 binding curve?
sigmoidal, indicates positive cooperativity
What does positive cooperatively in Hb (a tetramer) mean?
binding at one site increases the affinity of the second site
the affinity changes
Without cooperativity, what is it impossible to do?
impossible to fully load oxygen in the lungs AND efficiently deliver oxygen to deep tissues
aka Hb following a hyperbolic curve cannot both bind fully in the lungs and release efficiently in deep tissues
What happens when oxygen binds to Fe?
-pulls Fe into porphyrin plane
-pulls to proximal His (93) toward porphyrin plane
-helix F with His 93 shifts position
-disrupts ion pair interactions between subunits
What happens to the entire molecule when oxygen binds to Fe?
the entire molecule flexes as it transitions from the deoxy to the oxy state
What is the hemoglobin molecular switch?
conformational changes in Hb are induced by oxygenation
when the F-helix is in the relaxed position, the Fe+2 pokes out of the heme and can bind O2
O2 binding will trap the F-helix in the relaxed position
What happens in the T-state?
O2 cannot bind due to low affinity state
