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53 Cards in this Set

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2 Most studied and best understood proteins?
Myoglobin and hemoglobin
Myoglobin and hemoglobin illustrate almost every aspect of the ?
most central of biochemical processes: the reversible binding of a ligand to a protein
Oxygen is _______ in aqueous solutions and _______ be carried to tissues in sufficient quantity if it is simply dissolved in blood serum
- poorly soluble

- can not
Diffusion of oxygen through tissues is also ineffective over distances greater than ...
- a few millimeters
The evolution of larger, multicellular animals depended on the evolution of
- proteins that could transport and store oxygen

* none of the A.A side chains in proteins is suited for reversible binding of oxygen molecules

* This role is filled by certain transition metals, among them iron and copper, that have a strongtendency to bind to oxygen
Multicellular organisms exploit the properties of metals, mainly Iron, for
Oxygen transport
Free iron promotes the formation of highly reactive oxygen species such as hydroxyl radicals that can
- damage DNA and other macromolecules

- Iron used in cells is therefore bound in forms that sequeter it and/or make it less reactive
In multicellular Organisms - especially those in which iron, in its oxygen-carrying capacity, must be transported over large distances - iron is often incorporated into
- a protein-bound prosthetic group called Heme
Heme consists of ?
a complex organic ring structure, protophyrin, to which is bound a single iron atom in its ferrous (FE+2) state
The iron atom has
- six coordination bonds, four to nitrogen atoms that are part of the flat porphyrin ring system and two perpendicular to the porphrin
The coordinated nitrogen atoms of the iron atom help prevent?
- conversion of the heme iron to the ferric (Fe+3) state
Iron in the Fe+2 state ______ to oxygen reversibly
- binds
Iron in the Fe+3 state ______ to oxygen reversibly
- Doesn't
Heme is found in a number of ___ ____ ____, as well as in some ......
- oxygen transporting proteins

- proteins, such as the cytochromes, that participate in oxidation-reduction (electron-transfer) rxns
Free heme molecules (heme not bound to proteins) leave Fe+2 with ...
- two "open" coordination bonds.
Simutaneous rxn of one O2 molecule with two free Heme molecules (or two free Fe+2) can result in irreversible conversion ...
- of Fe+2 to Fe+3
Simutaneous rxn of one O2 molecule with two free Heme molecules (or two free Fe+2) can result in irreversible conversion of Fe+2 to Fe+3. In heme-containing proteins, this rxn is prevented by
- sequestering each heme deep within the protein structure where access to the two open coordination bonds is restricted.

* One of these two coordination bonds is occupied by a side-chain nitrogen of a His residue.

* The other is the binding site for molecular oxygen (O2)
When oxygen binds, the electronic properties of heme iron ...
change
What accounts for the change in color from the dark purple of oxygen-depleted venous blood to the bright red of oxygen-rich arterial blood
When oxygen binds, the electronic properties of heme iron change
When a molecule of CO is bound to heme, O2 ___ _____, which is why CO is highly toxic to aerobic organisms
- is excluded
By surrounding and sequestering heme, oxygen-binding proteins regulate ..
the access of CO and other small molecules to the heme iron
Myoglobin is ?
a relatively simple oxygen-binding protein found in almost all mammal, primarily in muscle tissue
Some small molecules, such as carbon monoxide (CO) and nitric oxide (NO), coordinate to heme iron with ____ ________than O2 does
- greater affinity
As a transport protein, Myoglobin facilitates in _________ _________ muscle
oxygen diffusion
Myoglobin is particularly abundant in the muscles of diving mamals where it also has an
- oxygen-storage function for prolonged excursions underseas
Proteins very similar to myoglobin are _________ distributed
- widely distributed, occurring even in some single celled organisms
Myoglobin is a sinle polypeptide of __ A.A residues with ____ _______of Heme
- 153 A.A residues

- one molecule of Heme
Myoglobin is typical of the family of proteins called
Globins

- all of which have similar primary and tertiary structures
The Myoglobin is made up of ?
- eight Alpha helical segments connected by bends

* About 78% of the A.A residues in the protein are found in these alpha helices
THe fuction of mytoglobin depends on the protein's ability ...
not only to bind oxygen but also to release it when and where it is needed
The reversible binding of a protein (P) to a ligand (L) can be described by a simple equillibrium expression
P + L <~~~> PL
The Ka of the protein-ligand interactions can be described as
[PL]
Ka = ------
[P][L]
The term K[a] is an
association constant
The association constant K[a] provides a measure of
the affinity of the ligand L for the protein
K[a] had the units ?
m -1
A higher value of K[a] corresponds to a
higher affinity of the ligand for the protein
When the concentration of the ligand is much greater than the concentration of ligand-binding sites, the binding of the ligand by the protein
- does not appreciably change the concentration of
free (unbound) ligand- that is [L] remains constant.

*This condition is broadly applicable to most ligands that bind to proteins in cells and simplifies our description of the binding equilibrium
Small molecules can be covalently attached to large proteins in the lab, and in this form they may elicit an immune response. The small molecules are called
Haptens
The antibodies produced in response to protein-linked haptens will then . .
- bind to the same small molecules when they are free
The interactions of antibody and antigen are much better understood than
- the binding properties of T-cell receptors
The immune system must id and destroy pathogens, but it must also . .
- recognize and not destroy the normal proteins and cells of the host organism "self"
Detection of protein antigens in the host is mediated by ..
MHC (major histocompatibility complex) Proteins
MHC proteins bind ...... and ......
- peptide fragments of proteins digested in the cell

- present them on the outside surface of the cell
The peptides that MHC proteins bind to normally come from . . .
- the digestion of typical cellular proteins

* but during a viral infection, viral proteins are also digested and presented on the cell surface by MHC proteins
The peptides that MHC proteins bind to normally come from the digestion of typical cellular proteins, but during a viral infection viral proteins are . . .
- also digested and presented on the cell surface by MHC proteins
Peptide fragments from foreign proteins that are displayed by MHC proteins are the antigens the immune system recognizes as . .
non-self
T- cells receptors bind these fragments from ______ and launch the
- MHC proteins

-sebsequent steps of the immune response
There are two classes of MHC proteins which differ in
- their distribution among cell types and in the source of digested proteins whose peptides they display
Class I MHC facts
- found on the surface of almost all vertebrate cells

- produces up to six class I MHC protein variants, any two people are unlikely to be the same

- bind and display peptides derived from the proteolytic degradation and turnover of protein that occur randomly within the cell

- these peptides and MHC proteins are the recognition targets of the T-cells receptors of the T[c] cells in the cellular immune system
Each T[c] cell has many copies of only one T-cell receptor that is . . .
- specific for a particular class I MHC protein-peptide complex
To avoid creating a legion of T[c] cells that would set upon and destroy normal cells, the maturation of T[c] cells in the thymus includes . . .
- a stringent selection process that eliminates more thatn 95% of the developing T[c] cells, including those that might recognize and bind class I MHC proteins displaying peptides from cellular proteins of the organism itself
The T[c] cells that survive and mature are those with occur on the surfaces of a few types of specialized cells
- t-cell receptors that do not bind to the organism's own proteins
Each T[c] cell has many copies of only one T-cell receptor that is specific for a particular class I MHC protein-peptide complex, The result is
a population of cells that bind foreign peptides bound to class I MHC proteins of the host cell

* These binding interactions lead to the destruction of parasites and virus-infected cells