Amino acids and protein structure Flashcards
Describe the general structure of an alpha amino acid
C-H
N-H2: amine group
C-O2-H: carboxylic acid group
R: side chain/variable group
What are the charges on an alpha amino acid at pH 7?
Positive charge on N of the amine group
Negative charge across the O2 of the carboxylic acid group
What is the charge on a protonated alpha amino acid (i.e. below pH 5)?
Positive charge on N of the amine group
What form is an alpha amino acid in between pH 3 and pH 8?
Zwitterionic form
What is the charge on a deprotonated alpha amino acid (i.e. above pH 7)?
Negative charge across the O2 of the carboxylic acid group
Using ‘CO-R-(H)-N’ law, a clockwise CO-R-(H)-N is known as what type of isomer?
A D isomer
Using ‘CO-R-(H)-N’ law, an anticlockwise CO-R-(H)-N is known as what type of isomer?
An L isomer
What type of bond forms between 2 amino acids?
A peptide bond
How would we describe a C omega bond angle of 180 degrees?
Trans
Favoured
How would we describe a C omega bond angle of 0 degrees?
Cis
Disfavoured
Is the change from free rotation about the C-N bond to a planar C-N bond reversible or irreversible?
Reversible
Describe the C-N bond when there is free rotation
Single bond, no charge
Double bond on C=O
Describe the C-N bond when it is planar
Double bond, negative charge on the O, positive charge on the N
(Single bond on C-O)
Name some important bonds/interactions in protein structure in order of decreasing strength
Covalent bonds Ionic (electrostatic) interactions Hydrogen bonds Hydrophobic interactions Van der Waals forces
Define covalent bonds
Strong bond, arising from the sharing of one or more pairs of electrons between atoms
Define ionic (electrostatic) interactions
Between 2 charged groups
Define hydrogen bonds
Sharing of a hydrogen atom between 2 other atoms (= hydrogen donor and acceptor)
Define hydrophobic interactions
Tendency for ‘water-hating’ molecules to cluster together to exclude water
Define van der Waals forces
Non-specific attractive force when 2 atoms are in close proximity (0.3-0.4nm)
Give an example of where a disulphide bond could form
Between 2 cysteines
What type of reaction forms a disulphide bond?
Oxidation reaction
What type of reaction breaks a disulphide bond?
Reduction reaction
What is released when a disulphide bond forms between 2 cysteines?
2H+ ions
2e-
Use chemical equations to demonstrate how an ionic interaction works
HA + H2O A- + H3O+
HA+ A + H3O+
What is the equation for Ka?
Ka = ([A-][H3O+]) / ([HA])
OR
Ka = ([A][H3O+]) / ([HA+])
What is the equation for pKa?
pKa = -log(Ka)
What is the equation for pH?
pH = -log(H3O+)
What is pKa?
The pH were 50% is ionised
What does a low pKa indicate?
Acidic
What can ionic interactions occur between?
Negative (acid) charged side chains - negatively charged, hydrophilic residues
Positive (basic) charged side chains - positively charged, hydrophilic residues
What is significant about ionic interactions?
Between charged groups
Positive attracts negative
Importance of environment
What is the distance between hydrogen-bond donors and acceptors?
~2.8 An = 0.28 nm
Give examples of hydrogen-bond donor and acceptor interactions
(-)dipole - (+)dipole _ (-)dipole N-H_N N-H_O O-H_N O-H_O
What is significant about hydrogen bonds?
They are directional, weakening as the (donor-H-lone pair) becomes less linear
What do 4 sp3 hybrid orbitals form?
A tetrahedron
Give examples of amino acids with side chains that can form hydrogen bonds
Residues with polar groups: Asparagine Cysteine Glutamine Neutral histidine Serine Threonine Tryptophan Tyrosine
What can’t hydrophobic groups form?
Hydrogen bonds
What do co-locating hydrophobic regions allow?
Water to maximise both hydrogen bonding and entropic potential
Give examples of amino acids with side chains that can form hydrophobic interactions
Nonpolar, hydrophobic residues Alanine Isoleucine Glycine Leucine Methionine Phenylalanine Proline Valine
In terms of van der Waals forces, what does a positive charge cause?
An induced dipole on a neighbouring atom
In terms of van der Waals forces, what does an induced dipole cause?
Mutually induced dipoles (transient) on neighbouring atoms
Define primary structure
The sequence of amino acids linked by covalent peptide bonds. Amino (N-) and carboxy (C-) termini.
Why is the peptide group rigid and planar?
Because the carbon-nitrogen bond has partial double-bond character. Also:
Peptide has dipole
Peptide N is a hydrogen bond donor, the carbonyl O an acceptor
Where is there freedom of rotation about bonds?
Either side of C alpha - dihedrals phi and psi
Define secondary structure
Regular structural motifs alpha-helix and beta-strand/sheet
H-bonding between -NH and -CO groups in protein backbone
Describe the properties of an alpha-helix
The peptide N is a hydrogen bond donor, the carbonyl O an acceptor
Main chain carbonyl group is H-bonded to main chain amino group four residues away
All polar groups of main chain are H-bonded so compatible with hydrophobic environment inside a protein, e.g. can have hydrophobic one side and hydrophilic the other side
At what ends are the positive and negative dipoles of the alpha-helix?
Positive dipole is at the N-terminal end
Negative dipole is at the C-terminal end
What binds to the heme group of myoglobin?
An iron atom
What secondary structural make up myoglobin?
Helix-turn-helix
Which side of the Ramachandran plot do beta-strands and alpha-helices lie?
Beta-strands at the top left
Alpha-helices at the bottom left
What is the Ramchandran plot a plot of?
psi vs. phi
In what orientation can beta-sheets lie?
Parallel or antiparallel
How do beta-strands combine and give and example of a molecule where this combination may occur?
In various ways with both parallel and antiparallel parts in a sheet
E.g. in part of an antibody molecule
What are the various ways secondary structures combine known as?
Motifs
What can the hairpin be extended to form?
The Greek-key
What forms the beta-alpha-beta motif? And what can this motif form?
The simple combination of a beta-sheet and a helix forms the motif
The motif can form larger structures, e.g. the TIM barrel
Is the barrel structure common or uncommon?
Very common, as it provides a good structural scaffold for forming an active site in an enzyme
In the right-handed beta-alpha-beta unit, where does the helix lie ?
The helix lies above the plane of the strands
Beta-alpha-beta can double up to form what?
Nucleotide binding domain with signature g-x-g-x-x-g found in e.g. dehydrogenases
(Known as the Rossman fold)
Describe how a barrel might form
Trimer of left-handed beta-helices with alpha-helical region at C-terminus
Alpha-helices can also combine to form what? And give an example of one of the most important
Form motifs
One of the most important is the helix-turn-helix that has been found in many DNA-binding proteins
Where can you fins a similar helix-loop-helix motif?
The calcium-binding EF hand
Electronegative oxygens around Ca2+
Give examples of other motifs worth knowing about
The four-helix-bundle
The leucine zipper
What might proteins also have bound?
Metal ions, they may be important for the structure, and an example is the zinc finger found in DNA binding proteins
What can some large polypeptides fold into?
Domains
What is the fundamental unit of tertiary structure?
Domains
Define domain
A polypeptide chain or part of a polypeptide chain that can fold independently into a stable tertiary structure
What are domains also units of?
Also units of function, they may be recognisable from an analysis of sequence
May be subunits, if the oligomeric protein consists of more than one chain
Give examples of a domain
SH2 (Src-homology-2) and SH3 (Src-homology-3) domains
Define tertiary structure
Folding of polypeptide, stabilised by side chain interactions (covalent, ionic, H-bonding, hydrophobic, van der Waals)
Describe the properties of the amino acids in myoglobin
Hydrophilic and polar amino acids on the outside, hydrophobic amino acids on the inside
Describe the distribution of amino acids in a membrane protein
‘Inside out’
Water-filled hydrophobic channel
Largely hydrophobic exterior
Define quaternary structure
Associations between polypeptides - multisubunit molecules, e.g. Hb.
Mainly side chain interactions (covalent, ionic, H-bonding, hydrophobic, van der Waals)
Where do disulphide bonds primarily occur? And give an example of a biological molecule that contains disulphide bonds
Primarily occur in extracellular proteins
Can be intra- or intersubunit
Can be found in insulin
