9.5 Protein-Ligand Interactions

Function of hemoglobin

transports molecular oxygen from lung to tissue, then transports CO2 from tissue to lung

Function of myoglobin

stores molecular oxygen in tissue

Similarities of Myoglobin and Hemoglobin in structures

similar tertiary structure but different primary structures

Myoglobin and hemoglobin are what kind of proteins that bind to…

heme-proteins; oxygen

Myoglobin and each hemoglobin monomer is a

single polypeptide composed of 8 helices

In each polypeptide chain, a heme group is bound between helix

E and F

Myoglobin is a single polypeptide chain of ___ amino acid residues

153

Tertiary structure of 8 right-handed a-helices with a hydrophobic pocket, which forms a

protective sheath for a heme group with iron atom in the middle

Heme iron bonded to HIs on helix _, with an open O2 binding site between iron and His on helix _

E; F

Monomeric heme protein found mainly in ____ tissue; serves as

muscle; an intracellular storage site for oxygen

Myoglobin binds to O2 reversibly:

Mb + O2 ←→ MbO2

During periods of oxygen depletion, oxy-myoglobin releases

its bound oxygen which is then used in metabolism

Myoglobin’s secondary structure is unusual, it contains __% of a-helices

78

Tertiary structure of myoglobin is typically

water soluble globular protein

Each heme contains

one central, coordinately bound, iron atom that is normally in the Fe2+, or ferrous oxidation state

Oxygen carried by heme-proteins (both myoglobin and hemoglobin) is bound directly to

ferrous iron atom of the heme prosthetic group

FE2+ is _____ coordinated

octahedral

Heme groups is located in a crevice between

E and F helices, except for non-polar R groups surround the heme

Fe2+ covalently bonded to the

imidazole group of histidine 93 (F8)

O2 is held on the other side by

histidine 64 (E7)

Heme protein conjugate is strongly stabilized by

hydrophobic interactions between the heme tetrapyrrole ring system and hydrophobic R groups on the interior of the cleft in the protein

Heme protein conjugate is stabilized further by

coordination of the iron atom with the nitrogen atom of the histidine R group, located above the plane of the heme ring on the F-helix

In oxygen-bound myoglobin (oxy-Mb) or oxygen-bound hemoglobin (oxy-HB), the remaining bonding site on the iron (6th coordinate position) is occupied by

the oxygen O2

O2 binding is stabilized by ________________ on the E-helix

second histidine residue (distal His)

Heme and protein protect Fe2+ from

irreversible oxidation to Fe3+

T/F Carbon monoxide binds to heme iron more strongly than oxygen

TRUE

Preferential binding of carbon monoxide to heme iron is largely responsible for

the asphyxiation in carbon monoxide poisoning

CO binds to free heme _____ times better than O2

20,000

CO binds ___ times better than O2 to hemoglobin

250

O2 binds to free heme at ____, but CO binds to free heme ____ to the heme plane

an angle; perpendicular

When O2 binds to the heme in Mb or Hb, binds at _____ ________, because the perpendicular arrangement is blocked by ___ ___

slight angle; His E7

Hemoglobin is tetramer of

four polypeptide chains

Hemoglobin consists of two identical a chains (___ AA residues) and two idential B chains (___ AA residues)

141, 146

Each chain has a ___ group, hence ___ O2 can bind to each Hb

heme, four

Each subunit of a hemoglobin tetramer has a

heme prosthetic group identical to that described for myoglobin

The quaternary structure of hemoglobin leads to physiologically important ____ interactions between the subunits. Property lacking in monomeric myoglobin, which is otherwise very similar to a subunit of hemoglobin

allosteric

Heme-binding residues (___ and ____) have ____ _____ in all three polypeptide chains

His E7 and F8

Although three polypeptide chains of Mb, a-Hb, and B-Hb only have __ identical AA residues, the structure of myoglobin and the monomer subunits of hemoglobin are very similar

27