Chapter 3
Proteins
Protein structure (pages 125- 148; figures 3-1 to 3-28, 3-35)
1.
The Shape and structure of proteins
primary, secondary, tertiary, quaternary structure of proteins
primary structure – sequence of amino acids; peptide bond
secondary structures – -helix and -sheet; hydrogen bonds
tertiary structure – noncovalent bonds; folding of proteins into a conformation of lowest
energy
quaternary structure – noncovalent bonds
2.
Protein domain arrangements (module)
“In-line” – e.g. fibronectin type I, immunoglobulin
“plug-in” – e.g. SH2 domain, kringle
3.
Proteins can be classified into many families
4.
Sequence searches can identify close relatives
Generally a 30% identity suggests relatedness
5.
Domain shuffling
6.
Quaternary structure of proteins
Weak bonds
“head to head” arrangement – dimmers
Single binding site
“head to tail” arrangement – multimers
2 binding sites
Ring – neuraminidase
Filaments – actin
7.
Proteins that have elongated, fibrous shapes
Fibrous proteins
e.g. alpha-keratin – intracellular
collagen – extracellular
Elastic fibers
e.g. elastin – extracellular
8.
Disulfide bonds stabilize extracellular proteins
form in the ER
Protein function (pages 152-178; figures 3-36 to 3-67)
9.
Selective binding of proteins to other molecules
Binding may be weak or tight
Specificity
Weak bonds – ionic (electrostatic), hydrogen, van der Waals, hydrophobic
Binding site
10.
Surface conformation of a protein determines its chemistry
Interaction of neighboring parts of the polypeptide chain may restrict the access of
water molecules to the protein’s binding site
- Clustering of neighboring polar amino acid side chains can alter their reactivity e.g.
clustering of negatively charged side chains increases affinity of a positively charged ion
11.
The equilibrium constant measures binding strength
12.
cAMP binding proteins – brings about conformational changes
DNA binding proteins
Enzymes (e.g. PKA)
Ion channels
13.
Serine proteases – “catalytic triad” – chemistry at an active site
14.
SH2 domain – example of conserved binding sites
Protein protein interactions – surface string, helix-helix, surface-surface
15.
Antibody molecules – specificity and affinity of binding sites
16.
Equilibrium constant (K); Vmax; Km
Turnover number = Vmax/enzyme concentration
17.
Transition state; catalytic antibodies
Stabilization of a transition state by an antibody creates an enzyme
18.
Lysozyme – example of acid-base catalysis
Distortion of bound substrate
Negatively charged Asp attacks the C1 of the distorted sugar; Glu donates a proton to
the oxygen in the glycosidic bond; water molecule displaces the Asp
19.
General strategies for enzyme catalysis
- Carbamoyl phosphate synthetase - molecular tunnels that connect active sites
Glutamine  NH3  carboxyphosphate  carbamate  carbamoyl phosphate
- Pyruvate dehydrogenase complex – multienzyme complex
- Aspartate transcarbamoylase – allosteric transition
- Protein kinases/protein phosphatases – protein phosphorylation
- Cdk – integrating protein