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53 Cards in this Set
- Front
- Back
2 Most studied and best understood proteins?
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Myoglobin and hemoglobin
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Myoglobin and hemoglobin illustrate almost every aspect of the ?
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most central of biochemical processes: the reversible binding of a ligand to a protein
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Oxygen is _______ in aqueous solutions and _______ be carried to tissues in sufficient quantity if it is simply dissolved in blood serum
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- poorly soluble
- can not |
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Diffusion of oxygen through tissues is also ineffective over distances greater than ...
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- a few millimeters
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The evolution of larger, multicellular animals depended on the evolution of
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- 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 |
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Multicellular organisms exploit the properties of metals, mainly Iron, for
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Oxygen transport
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Free iron promotes the formation of highly reactive oxygen species such as hydroxyl radicals that can
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- damage DNA and other macromolecules
- Iron used in cells is therefore bound in forms that sequeter it and/or make it less reactive |
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In multicellular Organisms - especially those in which iron, in its oxygen-carrying capacity, must be transported over large distances - iron is often incorporated into
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- a protein-bound prosthetic group called Heme
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Heme consists of ?
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a complex organic ring structure, protophyrin, to which is bound a single iron atom in its ferrous (FE+2) state
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The iron atom has
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- six coordination bonds, four to nitrogen atoms that are part of the flat porphyrin ring system and two perpendicular to the porphrin
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The coordinated nitrogen atoms of the iron atom help prevent?
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- conversion of the heme iron to the ferric (Fe+3) state
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Iron in the Fe+2 state ______ to oxygen reversibly
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- binds
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Iron in the Fe+3 state ______ to oxygen reversibly
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- Doesn't
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Heme is found in a number of ___ ____ ____, as well as in some ......
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- oxygen transporting proteins
- proteins, such as the cytochromes, that participate in oxidation-reduction (electron-transfer) rxns |
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Free heme molecules (heme not bound to proteins) leave Fe+2 with ...
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- two "open" coordination bonds.
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Simutaneous rxn of one O2 molecule with two free Heme molecules (or two free Fe+2) can result in irreversible conversion ...
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- of Fe+2 to Fe+3
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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
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- 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) |
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When oxygen binds, the electronic properties of heme iron ...
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change
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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
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When oxygen binds, the electronic properties of heme iron change
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When a molecule of CO is bound to heme, O2 ___ _____, which is why CO is highly toxic to aerobic organisms
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- is excluded
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By surrounding and sequestering heme, oxygen-binding proteins regulate ..
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the access of CO and other small molecules to the heme iron
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Myoglobin is ?
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a relatively simple oxygen-binding protein found in almost all mammal, primarily in muscle tissue
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Some small molecules, such as carbon monoxide (CO) and nitric oxide (NO), coordinate to heme iron with ____ ________than O2 does
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- greater affinity
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As a transport protein, Myoglobin facilitates in _________ _________ muscle
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oxygen diffusion
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Myoglobin is particularly abundant in the muscles of diving mamals where it also has an
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- oxygen-storage function for prolonged excursions underseas
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Proteins very similar to myoglobin are _________ distributed
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- widely distributed, occurring even in some single celled organisms
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Myoglobin is a sinle polypeptide of __ A.A residues with ____ _______of Heme
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- 153 A.A residues
- one molecule of Heme |
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Myoglobin is typical of the family of proteins called
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Globins
- all of which have similar primary and tertiary structures |
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The Myoglobin is made up of ?
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- eight Alpha helical segments connected by bends
* About 78% of the A.A residues in the protein are found in these alpha helices |
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THe fuction of mytoglobin depends on the protein's ability ...
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not only to bind oxygen but also to release it when and where it is needed
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The reversible binding of a protein (P) to a ligand (L) can be described by a simple equillibrium expression
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P + L <~~~> PL
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The Ka of the protein-ligand interactions can be described as
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[PL]
Ka = ------ [P][L] |
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The term K[a] is an
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association constant
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The association constant K[a] provides a measure of
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the affinity of the ligand L for the protein
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K[a] had the units ?
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m -1
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A higher value of K[a] corresponds to a
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higher affinity of the ligand for the protein
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When the concentration of the ligand is much greater than the concentration of ligand-binding sites, the binding of the ligand by the protein
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- 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 |
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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
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Haptens
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The antibodies produced in response to protein-linked haptens will then . .
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- bind to the same small molecules when they are free
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The interactions of antibody and antigen are much better understood than
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- the binding properties of T-cell receptors
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The immune system must id and destroy pathogens, but it must also . .
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- recognize and not destroy the normal proteins and cells of the host organism "self"
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Detection of protein antigens in the host is mediated by ..
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MHC (major histocompatibility complex) Proteins
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MHC proteins bind ...... and ......
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- peptide fragments of proteins digested in the cell
- present them on the outside surface of the cell |
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The peptides that MHC proteins bind to normally come from . . .
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- 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 |
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The peptides that MHC proteins bind to normally come from the digestion of typical cellular proteins, but during a viral infection viral proteins are . . .
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- also digested and presented on the cell surface by MHC proteins
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Peptide fragments from foreign proteins that are displayed by MHC proteins are the antigens the immune system recognizes as . .
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non-self
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T- cells receptors bind these fragments from ______ and launch the
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- MHC proteins
-sebsequent steps of the immune response |
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There are two classes of MHC proteins which differ in
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- their distribution among cell types and in the source of digested proteins whose peptides they display
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Class I MHC facts
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- 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 |
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Each T[c] cell has many copies of only one T-cell receptor that is . . .
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- specific for a particular class I MHC protein-peptide complex
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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 . . .
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- 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
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The T[c] cells that survive and mature are those with occur on the surfaces of a few types of specialized cells
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- t-cell receptors that do not bind to the organism's own proteins
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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
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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 |