Protein Structure and Functions

Flashcards for reviewing protein structure and function lecture notes.

Proteins

Proteins are of primary importance and make up more than half the dry weight of most organisms.

Conformation

Spatial relationship of every atom in a molecule; interconversion occurs via retention of configuration, generally via rotation about a single bond.

Configuration

Geometric relationship between a given set of atoms; interconversion requires breaking (and removing) of covalent bonds.

Primary Structure of Proteins

The linear sequence of amino acids in the polypeptide chain, held together by peptide bonds and disulfide bonds.

Peptide Bond

The most important covalent bond, which determines the primary structure of proteins, formed by condensation.

Secondary Structure of Proteins

Regular arrangements of amino acids (3-30 AAs) located near each other in the linear sequence, based on H-bonding.

Alpha Helix

Spiral backbone of amino acids stabilized by extensive intrachain hydrogen bonding between the peptide-bond carbonyl O and amide H.

Beta Structures

Composed of two or more peptide chains (β-strands) (intrachain bonds), or of segments of PP chains (interchain bonds) fully extended (parallel or antiparallel) and all of the peptide bond components are involved in H-bonding

Beta-Bends

Reverse the direction of a PP chain, to form a compact, globular shape, usually found on the surface of protein molecules, generally composed of 4 AAs (Pro, Gly), stabilized by H- and ionic bonds

Supersecondary Structures (Motifs)

Combination of secondary structure elements (α-helices, β-structures, connected by non-repetitive secondary structural elements).

Tertiary Structure

The overall three-dimensional arrangement of all atoms in a protein, referring both to the folding of domains and the final arrangement of domains in the polypeptide.

Domain

The basic units of structure and function in a polypeptide chain.

Disulfide Bonds

A covalent linkage formed from the –SH groups of each of two cysteine residues, contributing to the stability of the 3-D shape and preventing denaturation.

Quaternary Structure

The arrangement of polypeptide chains (subunits) into a single protein (a multisubunit protein) consisting of two or more polypeptide chains that may be structurally identical or totally unrelated (oligomer, multimer).

Protein Family

Proteins with significant primary sequence similarity, and/or with similar structure and function, strong evolutionary relationship.

Superfamilies

Two or more families with little primary sequence similarity, contain the same major structural motif and functional similarities.

Denaturation

Unfolding and disorganization of a protein's secondary and tertiary structures without hydrolysis of peptide bonds, often leading to precipitation.

Amyloidosis

Accumulation of spontaneously aggregating proteins – amyloids (long, fibrillar protein assemblies consisting of β-pleated sheets) is implicated in neurodegenerative disorders.

Alzheimer's Disease

The Aβ peptide aggregates, generating the amyloid that is found in the brain parenchyma and around blood vessels

Prion Diseases

Diseases caused by misfolded Prion proteins that cause neuron degeneration due to accumulation of insoluble amyloid fibers.

Prion

Infectious agent that has been traced to a single protein (Mr 28,000), not associated with detectable nucleic acid.

Protein Classification

Proteins are classified into two major groups: Fibrous proteins with polypeptide chains arranged in long strands or sheets and Globular proteins with polypeptide chains folded into a spherical or globular shape.

Globular Heme Proteins - Hemoglobin

Proteins that contain heme as a tightly bound prosthetic group carrying oxygen from the lungs to tissues. in erythrocytes, transports О2 from the lungs to the tissues and СО2 and Н+ from the tissues to the lungs; transports and releases NO in the blood vessels.

Myoglobin

Globular Hemprotein, О2 reservoir and an oxygen carrier within the myocytes for ATP synthesis when energy is highly consumed

Heme

Consists of a complex organic ring structure, protoporphyrin, to which an iron atom in its ferrous (Fe2+ ) state is bound

Quaternary Structure of Hb

Hb is built of 2 identical dimers - ()1 and ()2
The polypeptide chains within the dimers are held tightly
together by numerous hydrophobic interactions, as well as
ionic and hydrogen bonds.

Structural Difference Between Mb and Hb

Hb – quaternary structure, 4 PP chains Мb – 1 PP chain, tertiary structure

Oxygen Dissociation Curve

A plot of degree of saturation (Y) measured at different partial pressures of oxygen (рО2).

Bohr Effect

“О2 release from Hb at lowered рН and increased СО2 concentration in the tissues”.

2,3-Bisphosphoglycerate (2,3-BPG)

Reduces the Hb affinity for oxygen, which is released from Hb.

HbF

HbA sinthesis starts at the 8th month of pregnancy and HbA gradually replaces HbF. BPG binds more weakly to HbF than to HbA.

Hb A1C

Under physiologic conditions, HbA is slowly and nonenzymically glycosylated, the extent of glycosylation being dependent on the plasma concentration of glucose.

Hemoglobinopathies

Synthesis of structurally abnormal hemoglobins, reduced Hb solubility, point mutation in the gene coding for β chain

Thalassemias

the synthesis of either the - or β-globin chain is defective. α - Thalassemias, Reduced synthesis of α-chains

Methemoglobinemias

Oxidation of Fe2+ to Fe3+ , inability to bind О2 ,chocolate cyanosis

General Characteristics of Fibrous Proteins

Share properties that give strength and/or flexibility to the structures in which they occur. The fundamental structural unit is a simple repeating element of secondary structure, mainly β structures, less α-helices.

Collagen

Family of similar, rigid, insoluble proteins: more than twenty collagen types, as well as additional proteins that have collagen-like domains and Comprises 25% of all body proteins

Collagen Structure

Built from 3 α PP chains (in various combinations, each approximately 1000 AAs long), which form a triple helix

Elastin

A connective tissue protein with rubber-like properties found in the lungs, the walls of large arteries, and elastic ligaments

Enzymes

Enzymes: • Biocatalysts - increase the rate of chemical reactions in the cell/body without being changed in the overall process

Cofactors

Vitamins and their derivatives – Most are synthesized in plants and can be taken from the food

Enzyme Classes

Oxidoreductases – Catalyze oxidation-reduction reactions. Transferases - Catalyze transfer of groups Hydrolases - Catalyze cleavage of bonds by action of water Lyases (synthases) – Catalyse cleavage of bonds. The reverse reaction is also possible (to create bonds in the reverse direction) Isomerases – Isomerization reactions Ligases (synthetases) - Catalyze formation of covalent bonds, Require ATP as an energy provider

Km (Michaelis Menten Constant)

Is characteristic of an enzyme and its particular substrate, Reflects the affinity of the enzyme for the substrate, Numerically small Km reflects high affinity and vice versa

Vmax (Maximum Velocity)

Velocity at which all active sites are saturated with substrate molecules, Depends on enzyme concentration [E], Reflects the quantity of the active enzyme at a given moment

Limited Proteolysis

Enzymes are synthesized and secreted in non-active form (proenzymes, zymogenes) and Examples: • Digestive enzymes • Coagulation factors • Anticoagulation factors • Complement system members

Reversible inhibitors

Binds to the enzyme through noncovalent bonds - Competitive, Noncompetitive

Allosteric Enzymes

Regulatory enzymes: •Located at the beginning or at the end of the metabolic pathways

Isoenzymes

They catalyze equal reactions, Have equal substrate and cofactor specificity, Different enzyme forms can differ in: • Amino acid sequence > Different physical and chemical properties (electrophoretic mobility, pH optimum etc.) • Km for the substrate and/or for the cofactor • Regulation (may have different activators and/or inhibitors)

Nonfunctional Plasma Enzymes

Normally are not present in plasma or are present in very small quantities, In case of tissue damage they appear in plasma

Bioenergetics

Bioenergetics -Describes the transfer and utilization of energy in biologic systems It makes use of a few basic ideas from the field of thermodynamics, particularly the concept of free energy (G)

Free Energy (G)

The free energy is this part of the potential energy of the reactants, which can be used to carry out work at a time when the system is oriented towards establishing an equilibrium. -G: spontaneous process, a measure of the maximum amount of work that can be done if the reaction is coupled to a system capable of doing work

Exergonic and Endergonic Reaction

-G: Exergonic versus +G: Endergonic

Bioligical systems are open systems

G0 - is the standard free energy change

ATP

ATP - a molecule of adenosine (adenine + ribose) to which three phosphate groups are attached

Redox Proccesses

Oxidation (loss of electrons) of one compound is always accompanied by reduction (gain of electrons) of a second substance.

Redox pairs

The standard reduction potential (E°) of the Fe depends on the type of center and its interaction with the associated protein.

Electron Transport Chain

NADH and FADH2 can donate a pair of electrons to a specialized set of electron transporters, collectively called electron transport chains. During transfer down the chain the electrons loose part of their free energy Part of this energy may be captured and stored in the form of ATP in a process called oxidative phosphorilation.

Inhibitors of of the electron transport

Prevent the passage of electrons by binding to a component of the chain, blocking the oxidation/ reduction reaction.

The P/O ratios (coefficient of oxidative phosphorylation)

The P/O ratio is the number of ATPs made for each O atom
consumed by mitochondrial respiration.

NADH

The transport of reducing equivalents requires dehydrogenases on both sides of the membrane and appropriate substrates

Biological oxidation

Monooxygenases -Insert 1 atom О into the molecule of the substrate, and the second atom is reduced to water. Dioxygenases - Insert 2 О atoms into the substrate molecule

Cytochrome P450 Monooxygenase

System - Most abundant in ER of liver cells, consists of a Cytochrome P450 monooxygenase, Reaction (hydroxylation reaction), and cofactor (NADPH)

Free Radicals

Atoms, molecules or ions that have unpaired electrons

Oxidative Stress

impaired balance between pro-oxidants and antioxidants potentially leading to injury

Oxidative Stress and Diseases

• Inflammatory diseases • Atherosclerosis • Diabetes • Rheumatoid arthritis • Alcoholism • Retinopathy • Lung diseases • Parkinson disease • Aging • Cancer • Many others

Antioxidants

Antioxidants are substances that when present at low concentrations, compared to the substrate, significantly decrease or prevent oxidation of the given substrate”, antioxidant defenses include - Vitamins, Enzymes, other

Metabolism

The sum of all the chemical changes occurring in a cell, a tissue, or the body. - > Provides Specialized molecules and ensures their degradation

Catabolic and anabolic pathways are not just reverse pathways

Catabolism -Anabolic pathways do not overlap, Anabolic reacion combine small molecules to form complex molecules with greater size and complex structure and functions.