amino acids , peptides and proteins (Dr Hawthorne) Flashcards
amino acids
they are the building blocks of proteins and peptides which makes them proteinogenic
peptides contain up to 50 amino acids + proteins but there can be more than 50 ( there can be several thousand amino acids in large complex proteins )
amino acids are organic compounds that contain an amine group ( NH2) and a carboxyl group ( COOH) along side an R group side chain which is specific to each amino acid .
the key elements to amino acids are C,H,N,O but other elements are found in the side chains such a sulphur.
there is about 500 naturally occurring amino acids but only 20 appear in genetic code ( proteinogenic)
Naming amino acids
amino acid : 3 letter abbreviation : 1 letter abbreviation:
alanine ala A
arginine arg R
asparigine asn. N
aspartic acid. asp D
cysteine cys C
glutamic acid Glu E
glutamine gln Q
Glycine. gly G
Histidine His H
isoleucine ile. I
Leucine Leu L
lysine Lys. K
methionine. Met M
phenylalanine. Phe F
Proline Pro P
Serine Ser S
Threonine. Thr T
Tryptophan. Trp W
Tyrosine Tyr Y
Valine Val V
The genetic code - DNA to amino acid
Twenty amino acids are encoded directly by tripletcodonsin thegenetic code
Most amino acids have more than 1 codon – some exceptions
Met (AUG is the start codon and therefore first amino acid on ALL proteins is Met) and Trp
3 stop codons – signals the end of a sequence
Genetic code is degenerate
isomerism
with the exception of glycine , all amino acids adopt the L configuration
D amino acids are very rarely found in proteins
Side chains of amino acids ( R group)
The R group is very important
Amino acids are classified by thepropertiesof their R group into four groups
Non-polar
Polar uncharged
Polar charged – basic or acidic
Non polar amino acids
Gly has a proton for its R group – does not have a chiral centre
Ala, Val, Leu and Ile have non-cyclic alkyl hydrocarbon side chains
Met linear side chain that contains a sulphur
Phe and Trp have aromatic ring structures for side chains
Pro has a heterocyclic ring structure and is an imino acid, one of the N-H linkages is replaced by a N-C linkage - rigidity
Polar uncharged amino acids
These amino acids are relatively hydrophilic as they possess polar functional groups i.e. oxygen and nitrogen, which can participate in hydrogen bonding with water
Ser, Thr and Tyr have hydroxyl (OH) groups
Asn and Gln are derived from Asp and Glu where the carboxyl is modified to become an amide group
Cys has an SH group which is weakly acidic
Disulphide bond
Two thiol side chains (-SH) on cysteine amino acids can oxidise and cross-link to form a disulphide bond (-S-S-)
The two cysteines must be close together in the protein for this to occur
Hold the protein in its 3D conformation
Polar charged – basic amino acids
Lys and Arg have functional groups that are positively charged at pH 7
His has an imidazole group with a pKa 6.5, so it is not fully ionised at pH 7
This means the side chain of His can be fully charged, uncharged or partially charged depending on the precise situation
His can serve as either a proton donor or acceptor
Polar charged – acidic amino acids
Both Asp and Glu have carboxyl groups in their side chains which are negatively charged at pH 7
Asp pKa 3.46
Glu pKa 4.25
Zwitterions
A zwitterion contains the same number of positively and negatively charged functional groups but has an overall net zero charge
At pH values between the two pKavalues, the zwitterion predominates
Isoelectric point
At the exact midpoint between the two pKavalues, the amount of negative and positive ions exactly balance, so that average net charge of all forms present is zero
This pH is known as theisoelectric point,pI
pI=1/2(pKa1+ pKa2)
For amino acids with charged side chains, the pKaof the side chain is also involved
For example, for aspartate or glutamate with negative side chains, pI=1/2(pKa1+ pKa(R)), where pKa(R)is the side chain pKa
Proteogenic amino acids
These amino acids are components of peptides and proteins
Proteins are encoded by DNA which is transcribed into mRNA which is then translated into protein
Amino acids are joined together by a peptide bond
The 3D conformation of a protein is dependent on the R groups of the amino acids contained within it
Peptide bond formation
Amino acids can link together by a covalent bond between the -carboxyl end of one amino acid and the -amino end of another
Peptide bond (type of amide bond)
Peptide bond
The peptide bond is rigid and planar
Peptide backbone
Can be broken by hydrolysis (addition of water)
Digestive enzymes such as trypsin and elastase break down proteins in food by hydrolysing the peptide bonds
Non-proteinogenic amino acids
Either not found in proteins or not produced directly from the genetic code
Examples not found in proteins
GABA - neurotransmitter
Examples not produced directly from the genetic code
Formed by post-translational modification
Hydroxyproline – formed by hydroxylation of proline
Non-protein functions of amino acids
Tryptophanis a precursor of the neurotransmitterserotonin
Tyrosine(and its precursor phenylalanine) are precursors of thecatecholamineneurotransmittersdopamine,adrenalineandnoradrenaline
Glycineis a precursor ofporphyrinssuch ashaem
Arginineis a precursor ofnitric oxide
Protein structure
There are four levels of structure in proteins
Primary, secondary, tertiary and quaternary
Primary structure
Linear sequenceofamino acidsin apolypeptideorprotein
The primary structure of a protein is written as a string of letters starting from theamino-terminal (N) end to thecarboxyl-terminal (C) end
The primary structure of a protein is determined by thegenecorresponding to the protein
The sequence of a protein is unique to that protein, and defines the structure and function of the protein
Post-translational modifications
A wide variety of modifications can take place
The N-terminal amino group of a protein can be modified
Acetylation – addition of a –CH3 group
Phosphorylation - a phosphate group can be attached to the sidechain hydroxyl group of serine, threonine and tyrosine* most important modification *
Glycosylation – addition of sugars to sidechain hydroxyl groups of serine and threonine
secondary structure
Highly regular local structures on the polypeptide backbone chain
A polypeptide will spontaneously fold into a regular and defined shape – dependent on the primary structure
Three main types of secondary structure have been found in proteins
Alpha helix
Beta pleated sheet
Beta bend/turn
These secondary structures are defined by patterns ofhydrogen bondsbetween the polypeptide R groups
Alpha helix
Right hand-helixconformation in which every backboneN−Hgrouphydrogen bondsto the backboneC=Ogroup of theamino acidlocated three or fourresidues along the protein sequence
Most prevalent secondary structure in proteins
Beta pleated sheet
H-bonding is achieved by stretching out the polypeptide chain, and laying it side by side to form H-bonds between lengths of polypeptide chain
Beta bend/turn
Allows the peptide chain to reverse direction
Carbonyl C of one residue is H-bonded to the amide proton of a residue three residues away
Proline and glycine are prevalent in beta turns
Tertiary structure
3D structure created by a singlepolypeptide chain
The secondary structures are folded into a compact 3D structure
The folding is driven by thenon-specifichydrophobic interactions and the burial ofhydrophobic amino acids in the inside of the protein
The structure is stable only when the parts of aprotein domainare locked into place byspecifictertiary interactions, such assalt bridges, disulphide bonds and hydrogen bonds
Quaternary structure
3D structure consisting of the aggregation of two or more individual polypeptide chains that operate as a single functional unit (multimer)
It is stabilised by the same interactions that hold the tertiary structure together
Forms two types of proteins
Globular – polypeptide chains interact to form a spherical shape
Fibrous – polypeptide chains lie parallel to each other to form a fibre
Not found in all proteins
Globular protein - haemoglobin
Two alpha and two beta chains
Come together to form quaternary structure
Only active in quaternary form
Fibrous protein - collagen
Three linear polypeptides are twisted together and held by H-bonds
Provides strength to the collagen
