Chapter 3 Proteins Protein Structure (pages 125 148 Figures

chapter 3 proteins protein structure (pages 125- 148; figures 3-1 to 3-28, 3-35) 1. the shape and structure of proteins - primary,

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