week 1 Flashcards
Main Agents of Biological Function
Catalysis
– enolase (in the glycolytic pathway)
– DNA polymerase (in DNA replication)
Transport
– hemoglobin (transports O2 in the blood)
– lactose permease (transports lactose across the cell membrane)
Structure
– collagen (connective tissue)
– keratin (hair, nails, feathers, horns)
Motion
– myosin (muscle tissue)
– actin (muscle tissue, cell motility)
protein structure
primary structure: amino acid residues
secondary structure: a helix
tertiary structure: polypeptide chain
quaternary structure: assembled subunits
Amino Acids: Building Blocks of Protein
Proteins are linear heteropolymers of a-amino acids
* Amino acids have properties that are well-suited to
carry out a variety of biological functions
– Capacity to polymerize
– Useful acid-base properties – Varied physical properties
– Varied chemical functionality
* When combined in various sequences, the functional groups contribute to the function.
Most a-amino acids are chiral
- The a-carbon always has four
substituents and is tetrahedral - All(exceptproline)have:
– an acidic carboxyl group
– a basic amino group
– an a-hydrogen connected to the a- carbon - Thefourthsubstituent(R)is unique
– In glycine, the fourth substituent is also hydrogen
Amino Acids: Atom Naming
Organic nomenclature: start from one end * Biochemical designation:
– start from a-carbon and go down the R-group
Amino Acids: Classification
Common amino acids can be placed in five basic groups depending on their R substituents:
* Nonpolar, aliphatic (7) * Aromatic (3)
* Polar, uncharged (5)
* Positively charged (3) * Negatively charged (2)
Formation of Peptides
Peptides are small condensation products of amino acids
* They are “small” compared to proteins (Mw < 10 kDa)
Numbering (and naming) starts from the amino terminus
Usingfullaminoacidnames
– Serylglycyltyrosylalanylleucine
* Usingthethree-lettercodeabbreviation
– Ser-Gly-Tyr-Ala-Leu
* Forlongerpeptides(likeproteins)theone- letter code can be used
– SGYAL
Peptides: A Variety of Functions
- Hormones and pheromones – insulin (think sugar)
– oxytocin (think childbirth)
– sex-peptide (think fruit fly mating) - Neuropeptides
– substance P (pain mediator) - Antibiotics
– polymyxin B (for Gram – bacteria) – bacitracin (for Gram + bacteria) - Protection, e.g., toxins
– amanitin (mushrooms) – conotoxin (cone snails) – chlorotoxin (scorpions)
Structure of Proteins
Unlike most organic polymers,protein molecules adopt a specific three-dimensional conformation.
* Thisstructureisabletofulfillaspecific
biological function
* Thisstructureiscalledthenativefold
* The native fold has a large number of favorable interactions within the protein
* Thereisacostinconformationalentropyof folding the protein into one specific native fold
Favorable Interactions in Proteins
- Hydrophobic effect
– Release of water molecules from the structured solvation layer
around the molecule as protein folds increases the net entropy - Hydrogen bonds
– Interaction of N-H and C=O of the peptide bond leads to local
regular structures such as a-helices and b-sheets - London dispersion
– Medium-range weak attraction between all atoms contributes significantly to the stability in the interior of the protein - Electrostatic interactions
– Long-range strong interactions between permanently charged
groups
– Salt-bridges, esp. buried in the hydrophobic environment strongly stabilize the protein
Structure of the Peptide Bond
Structureoftheproteinispartiallydictated by the properties of the peptide bond
* The peptide bond is a resonance hybrid of two canonical structures
* The resonance causes the peptide bonds
– to be less reactive compared to esters, for example
– to be quite rigid and nearly planar
– to exhibit a large dipole moment in the
favored trans configuration
The Rigid Peptide Plane and the Partially Free Rotations
Rotationaroundthepeptidebondisnotpermitted
Rotation around bonds connected to the alpha carbon is permitted
f (phi): angle around the a-carbon—amide nitrogen bond
y (psi): angle around the a-carbon—carbonyl carbon bond
Inafullyextendedpolypeptide,both and are 180°
Distribution of f and y Dihedral Angles
Some f and y combinations are very unfavorable because of steric crowding of backbone atoms with other atoms in the backbone or side chains
* Some f and y combinations are more favorable because of chance to form favorable H-bonding interactions along the backbone
* A Ramachandran plot shows the distribution of f and y dihedral angles that are found in a protein
* shows the common secondary structure elements
* reveals regions with unusual backbone structure
Secondary Structures
Secondary structure refers to a local spatial arrangement of the polypeptide backbone
* Two regular arrangements are common:
* The a helix
– stabilized by hydrogen bonds between nearby residues
* The b sheet
– stabilized by hydrogen bonds between adjacent
segments that may not be nearby
* Irregular arrangement of the polypeptide chain
is called the random coil
The a Helix
Helical backbone is held together by hydrogen bonds between the backbone amides of an n and n+4 amino acids
* Right-handed helix with 3.6 residues (5.4 Å) per turn
* Peptide bonds are aligned roughly parallel with the helical axis
* Side chains point out and are roughly perpendicular to the helical axis
The a Helix: Top View
The inner diameter of the helix (no side chains) is about 4–5 Å
* Too small for anything to fit “inside”
* Theouterdiameterofthehelix(with sidechains) is 10–12 Å
* Happenstofitwellintothemajorgrooveof dsDNA
* Residues1and8alignnicelyontopofeachother
The Helix Dipole
- Recallthatthepeptidebondhas a strong dipole moment
– Carbonyl O negative – Amide H positive - Allpeptidebondsintheahelix have a similar orientation
- Theahelixhasalarge macroscopic dipole moment
- Negativelychargedresidues often occur near the positive end of the helix dipole
b Sheets
Theplanarityofthepeptidebondandtetrahedral geometry of the a-carbon create a pleated sheet-like structure
* Sheet-likearrangementofbackboneisheldtogetherby hydrogen bonds
Parallel and antiparallel B Sheets
Parallelorantiparallel
orientation of two chains within a sheet are possible
* InparallelbsheetstheH- bonded strands run in the same direction
– Resulting in bent H-bonds (weaker) (> 5 residues)
* Inantiparallelbsheetsthe H-bonded strands run in opposite directions
– Resulting in linear H-bonds (stronger)
b Turns
bturnsoccurfrequently whenever strands in b sheets change the direction
* The180°turnis accomplished over four amino acids
* Theturnisstabilizedbya hydrogen bond from a carbonyl oxygen to amide proton three residues down the sequence
Circular Dichroism (CD) Analysis
CDmeasuresthemolar absorption difference De of left- and right-circularly polarized light: De = eL – eR
* Chromophoresinthechiral environment produce characteristic signals
* CDsignalsfrompeptide bonds depend on the chain conformation
Protein Tertiary Structure
Tertiary structure refers to the overall spatial arrangement of atoms in a protein
* Stabilized by numerous weak interactions
between amino acid side chains.
- Largely hydrophobic and polar interactions
- Can be stabilized by disulfide bonds
* Interacting amino acids are not necessarily next to each other in the primary sequence.
Quaternary Structure
Foundinsomeproteins:hemoglobin(4units)
* Results from interactions between two or more polypeptide chains.
* Interactions include hydrogen bonding and disulfide bonds. Locks the complex into a specific geometry.
Structural and Functional advantages of Quaternary Association:
* Stability:reductionofsurfacetovolumeratio.
* Geneticeconomyandefficiency.
* Bringingcatalyticsitestogether.
* Cooperativity
