Biochemistry Exam 1: Protein Binding, Molecular Recognition, and Allostery

ligand

A molecule that binds specifically to a receptor site of another molecule (enzyme/protein in our case)

dissociation constant (Kd)

Concentration of free ligand needed to produce a state in which half of receptors are occupied; equal to L1/2; the lower the number, the better the binding affinity

heme prosthetic group

consists of protoporphyrin and an iron (II) ion in the center of a ring; a group non-covalently attached to myoglobin and hemoglobin that binds oxygen; the iron can bind bond in front and behind

proximal histidine

Imidazole ring of His occupying the fifth coordination site to which iron can bind in hemoglobin and myoglobin

sixth

oxygen binds at the ______ coordination site on the heme prosthetic group

ring plane

oxygen binding to the sixth position on a heme group moves the iron (Fe) in a ______ _______ position

hemoglobin

a tetramer of two alpha subunits and two beta subunits; each subunit has a heme group that is used to bind a transport oxygen through the body

store

myoglobin is used to _______ oxygen

allosteric; cooperativity

hemoglobin is an ________ protein that displays ________ in binding/releasing oxygen

allostery

binding of a ligand at one site affects the binding affinity at another site

homotropic effect

allosteric regulation by the same ligand; ex. oxygen binding a heme group effecting the binding affinity of an oxygen at a different heme group

heterotropic effect

allosteric regulation by a different ligand

positive cooperativity

first binding event increases affinity at remaining sites

recognized by sigmoidal binding curves

negative cooperativity

first binding event reduces affinity at remaining sites

T state

the state/position that hemoglobin proteins are in when they are currently holding oxygens that they would like to dump

R state

the state/position that hemoglobin proteins are in when they are able to pick up/bind new oxygen molecules to transport

deoxyhemoglobin

hemoglobin state associated with the T state; extensive alpha-beta dimer interaction (low affinity to bind oxygens); often found in tissues

oxyhemoglobin

hemoglobin state associated with the R state; loose alpha-beta dimer interaction (high affinity to bind oxygens); often found in the lungs

concerted

hemoglobin binding model where the protein only adopts two forms (R and T states); as more oxygens bind the favorability of hemoglobin transitioning from T to R states increases

sequential model

hemoglobin binding model where binding sites can change individually; binding of a oxygen puts that binding position into the R state and relaxes the other binding sights

planar

the position of the Fe in the heme group after binding O2 to the sixth coordination site; pulls the iron and proximal histidine up

binding

oxygen _____ results in a transformation for T state (deoxy-) to R state (oxyhemoglobin)

2,3-bisphosphoglycerate (2,3-BPG)

An allosteric regulator of oxygen binding by hemoglobin; binding tilts R and T equilibrium toward T state, making O2 release more favorable

His; Lys

2,3-BPG fits into the middle of hemoglobin and alloterically interacts with the beta subunits, specifically with the amino acids _____ 143 and _____ 82

carbonic anhydrase

enzyme that catalyzes the reaction between carbon dioxide and water to form carbonic acid

bicarbonate

product of CO2 respiration in RBCs, produced with H+ ions that lowers the pH of the body; how the majority of CO2 is transported to the lungs

the Bohr effect

the stimulation of oxygen release by CO2 and H+; lowering the pH of the body allows for salt bridges to form in hemoglobin and carbamate formation, stabilizing the T state

salt bridges

ionic bonds between ionized R groups of basic and acidic amino acids; in hemoglobin, these form at lowered pH to stabilize the T state

carbamate

amino termini structures that stabilize the T state; CO2 reacts with the a deprotonated N terminus to form this negatively charged molecule that can then go form salt bridges to stabilize the T state of hemoglobin

heterotropic

CO2 and H+ are ________ regulators of hemoglobin oxygen affinity

sickle cell anemia

a genetic disorder that causes abnormal hemoglobin, resulting in some red blood cells assuming an abnormal sickle shape

Val; 6

in sickle cell anemia, nonpolar ____ is substituted for Glu at position ___ of the beta chain

hydrophobic

Val residues on mutated sickle cell hemoglobin S interact with _______ patches on other Hb molecules, forming aggregates and blocking blood vessels, reducing oxygen transport

sigmoidal curve

shows slow and then rapid growth that slows back down when approaching the carrying capacity of hemoglobin