Chapter 5

Structure and Function of Protein

1. Amino acids

COO-NH3+ C

R

H

R--Different side chains, determin the properties of 20 amino acids.

Amino group Carboxylic acid group

structure

5.1 Protein Components

Aliphatic Aromatic Sulfur containing

Polar/uncharged basic/acidic

Hydrophobic- water fearing. non-polar side chains

Hydrophilic- water loving. polar, neutral chains negatively charged, positively charged

Classification

polypep

tide

protein

oligopeptid

e

dipeptide

tripeptide

decapeptid

e

3. Peptide and Polypeptide

2. Peptide bond Peptide Plane

Dihedral angle

5.2 Protein Structure

1. Primary structure

----linear sequence of amino acids in a

polypeptide chain

2. Secondary structure -helix

-strand, -sheet, -barrel, -turn

3. Tertiary Structure

Hemoglobin - an example of a four-subunit protein

4. Quaternary Structure

Animation

5. Bonds and Forces for Protein Structu

re

◆ Covalent bond

◆ Electrostatic interactions

◆ van der Waals interactions

◆ Hydrogen bonds

◆ Hydrophobic interactions

6. Denaturation and Renaturation of Prote

in

denaturat

ion

renaturat

ion

active inactive active

Animation

5.3 Protein Folding

1. Concept

Forces Involved in the Protein Foldi

ng

◆ Electrostatic interactions

◆ van der Waals interactions

◆ Hydrogen bonds

◆ Hydrophobic interactions

3. Models for Protein Folding

◆ Framework Model

◆ Hydrophobic Collapse Model

◆ Nuclear-Condensation Model

◆ Diffusion-Collision model

◆ Funnel or Energy-landsape models

DISEASEPROTEIN AFFECTED

MOLECULAR DEFECT

Cystic FibrosisCystic fibrosis transmembrane regulator (CFTR)

Misfolding and retention in the endoplamic reticulum, leading to degradation

Marfan Syndrome

Fibrillin Misfolding

NephrogenicDiabetesInsipidus

Vasopressin receptor or aquaporin water channel

Misfolding and retention in theendoplasmic reticulum

α-1-Antitrypsin Deficiency

Alpha-1-AntitrypsinMisfolding and retentionin the endoplasmic reticulum, leading toaggregation in cells of synthesis

Creutzfeldt-Jakob Disease

Prion proteinAggregation in brain (after protein release)

Alzheimers's Disease

Beta-amyloidAggregation in brain (after protein release)

5. Protein Misfolding and Diseases

5.4 Structure and Function of Enzyme

Most enzymes are proteins

J.B.Sumner J.H.Northrop

2. Classification of enzymes

Based on type of reaction

Oxidoreductase catalyze a redox reaction

Transferase transfer a functional group

Hydrolase cause hydrolysis reactions

Lyase break C-O,C-C or C-N bonds

Isomerase rearrange functional groups

Ligase join two molecules

1. Proteins play key roles in a living system

3. Structure of Enzyme

(1) Active site Catalytic site Binding site

(2) Specificity Group specificity Absolute specificity Stereo specificity Sequence specificity

4. Catalysis Mechanism

(1) Hypothesis/Theory

Lock and key model

Induced-fit model

Lock and key Theory

( 锁钥学说 )

Hermann Emil FischerThe Nobel Prize in Chemistry 1902

Induced –fit hypotheory

( 诱导契合假说 ) 1958

(1998 Albert Lasker Award )

Daniel KoshlandProfessor, Biochemistry and Molecular Biology, University of California, Berkeley

Induced-Fit Model of enzyme catalysis

(3) Features of catalytic reaction ▼high efficiency ▼specificity ▼be regulated ▼inactive easily

(4) Factors affecting enzyme activity Temperature pH Substrate concentration Enzyme concentration

(2) Steps in an enzymatic reaction

Summary

1. Peptide, polypeptide

2. Hierarchical protein structure.

3. Motifs and Domains of protein

4. Protein folding, misfolding and diseases

5. Protein functions and classification

6. Structure of enzyme and its specificity