Cooperativity & Enzymes

Cooperativity & Enzymes - *Ligand Binding and...

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*Ligand Binding and Cooperativity* Oxygen Binding to Hemoglobin as Example Compare oxygen binding to hemoglobin with oxygen binding to myoglobin moles O 2 bound Hb binds 4 O 2 with sigmoidal binding curve Mb binds 1 O 2 with hyperbolic binding curve pO 2 =pressure above sol’n Notice at low pO 2 Mb better O 2 binding
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% O 2 saturation Mb Hb veins lung and arteries pO 2 pO 2 (50%) for Hb = 26 torr pO 2 veins = 30 torr pO 2 lungs = 100 torr
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% O 2 saturation Mb Hb veins lung and arteries pO 2 Hb picks up O 2 in the lungs and delivers about 40% of the oxygen to tissue (veins). Mb helps remove the O 2 from the Hb to deliver oxygen to muscle tissue. Mb acts as a sort of “bucket brigade”.
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Why wouldn’t Mb or a simple molecule like Mb work in the circulatory system to transport O 2 ? can’t release much O 2 at 30 torr ( ) to deliver 40%, the O 2 pressure in tissue would have to be about 10 torr (dark red arrow ).This corresponds to very little O 2 in the tissue. so a molecule with a hyperbolic binding curve will not work. pO 2
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A sigmoidalbinding curve is required to dissociate O 2 properly and deliver O 2 . A sigmoidal binding curve implies a Cooperative Interaction.
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Cooperative Interaction Definition: Binding of one small molecule (ligand) affects the binding of others. binding of first O 2 is difficult. but makes the second binding of O 2 easier. third O 2 very easy. O 2 O 2 O 2 O 2 O 2 O 2 O 2 O 2 O 2 O 2
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In hemoglobin, the binding of O 2 to sites 2-4 is so much easier than the binding to the 1st site that Hb always has either 0 O 2 or 4 O 2 bound. Whenever first binding is difficult and this binding makes next ligand bindings easier, you always get a sigmoidal binding curve.
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What is the global structural basis for this binding cooperativity? the quaternary structure of Hb changes when O 2 binds. When oxygen binds to the deoxy form of Hb, some of the subunits rotate about 15 degrees.
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One consequence is that a large central cavity in deoxy Hb is converted to a smaller hole in the oxygenated Hb, the oxy-form. small large Binding of O 2 to the heme affects the conformation of distant parts of the protein and this change in conformation affects the binding of additional O 2 .
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Such a conformational change is called an Allosteric Conformational Change , a general term. What is the local trigger for this global conformational change in Hb?
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His F8 His F8 Fe heme Deoxy form (T) Oxy form (R) Fe O 2 O 2 binding pulls Fe +2 down, flattening the heme. His F8 shifting to the right is the trigger . This moves helix F8. F8 helix
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: The binding of oxygen relaxes conformation from the tense deoxy state to the relaxed oxy state. Note: The release of O
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Cooperativity & Enzymes - *Ligand Binding and...

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