Biochem Lecture 1: protein structure/function

what are proteins made up of?

Amino acids

what are the components of Amino Acids

alpha C bonded to a Hydrogen, amino group, carboxylic acid, and a R sidechain

Chirality

all different R groups attached to a carbon center

Why is Chirality important?

virtually all amino acids in proteins are L-stereomers, the bac cell wall has amino acids in D-steresomers, drugs can specifically target the cell wall

Drugs that mimic the D-conformation of Amino Acids

penicillin and its derivatives

Why is it important to synthesize a drug with predominantly one enantiomer?

To increase the drugs efficiency and/or to decrease the toxic effects due to the other chiral conformation

Hydrophilic AA

loves water: Serine, Threonine, Asparagine, Glutamine, Aspartic Acid, Glutamic acid, Arginine, Histidine, Cysteine

Hydrophobic Amino Acids

hates water: Alanine, isoleucine, Leucine, Valine, Phenylalanine, proline, Glycine

Aromatic Amino Acids

Tryptophan, Tyrosine, Phenylalanine

Charged Amino Acids

Arginine, Histidine, Aspartic acid, Lysine Glutamic acid

Polar Amino Acids

Interacts with water: Glutamine, Arginine, Lysine, Glutamine, Aspartate, Threonine, Cysteine, Histidine, Tyrosine, Asparagine, Serine

Which amino acid is not chiral?

Glycine, two H’s bonded

Which amino acid forms disulfide bonds?

Cysteine

Insulin protein

consists of 2 polypeptide chains stabilized by 3 disulfide bonds between cysteines

Special character of proline

only cyclized Amino Acid, restricts protein stability

Tryptophan derivated

Melatonin and serotonin

Tyrosine derivatives

DOPA→ treats some forms of dystonia

Dopamine

Norepinephrine

epinephrin→ treats cardiac arrest

Arginine derivatives

guanidoacetate, creatine, creatine phosphate, creatinine

formation of a dipeptide bond

condensation or dehydration reaction

What happens in people who Phenylketonuria (PKU)?

they lack the metabolizing enzyme phenylalanine hydroxylase, so the phenylalanine from aspartame in sodas cause problems with brain development and seizures

Protein sequence convention

Nt to Ct

why do alpha helixes form?

charges are not favorable, so the chain folds to form “bonds” with side chains

alpha helix structure

L-amino acids are right handed, regular backbone CO to NH (i→1+4) hydrogen bonds separated by 4 residues, H-bonds are parallel to helix long axis, one turn= 5.4 Angstroms, 3.6 residues

beta-sheet structure

zigzag backbone, H-bonds between adjacent segments of polypeptide chain, two conformations possible (antiparallel, parallel)

Antiparallel beta-sheets

Nt, Ct, Nt; more stable than parallel because of linear N-H…O-H bonds

parallel beta sheets

Nt, Nt, Nt; aligned main chain atoms, non-linear N-H… O-H bonds so less stable than antiparallel

Right handed connection between parallel beta strands

shorter than left, bend through smaller angles

Beta hairpin structure

main structural motif; beta-turn and a stabilizing interaction between sidechains of amino acids on beta- strands

beta turns

180⁰ turn involving 4 amino acids, Type 1 and type 2 which involves a glycine

What is a tertiary structure?

interaction between different secondary structural elements

Fibrous peptide

polypeptide chain arranged in long strands or sheets, usually consists of a single type of secondary structure and their tertiary structure is relatively simple, provides support, shape, and external protection to vertebrates. Also insoluble in water, high number of hydrophobic residues

Globular proteins

polypeptide chain folded into a spherical shape, contain several types of secondary and tertiary structures, enzymes and regulatory proteins

example of fibrous proteins

collagen in the tendons, cartilage, organic matrix of bone, cornea of the eye

Collagen structure

left-handed helix, 3 amino acids per turn, using a repeating tripeptide unit: Gly-X-Y (X is often proline, Y is often 4-hydroxyproline). Gly required for sharp turns, Proline and 4-Hyp allows sharp twisting

Why is Gly important in collagen?

Allows for tight junctions, mutating Gly to any other AA with a larger R will cause lethal diseases

Globular proteins

different segments of the polypeptide chain fold back on each other, generating a more compact shape than is seen in the fibrous proteins; enzymes, transport proteins, motor proteins, other proteins

Quarternary structure of globular proteins

3D arrangement of more than one polypeptide chain; hemoglobin

Hemoglobin binding

contains 4 polypeptide chains, binding one oxygen molecule by one subunit affects the oxygen binding of other three subunits

What are intrinsically disordered proteins (IDPs)

function in the absence of a defined 3D structure, 1/3 of proteins, characterized by high densities of charged AA residues, do not aggregate unlike other proteins b/c lack of hydrophobic core and high charge density. Allows the protein to bind to multiple partners b/c of lack of an ordered structure