Protein structure

Question 1

What are rotamers?

Answer 1

Rotamers - allowed arrangements of rotations in the side chain

Question 2

Why do we have non polar interactions at the surface?

Answer 2

• it needs to interact with other proteins so hydrophobic allows for interactions
• you want the protein to have marginal stability - you don’t want a brick

Question 3

What re the categories of proteins?

Answer 3

• Transmembrane
• Globular (water soluable)
  
  • enzymees, antibodies
  • focus of most lecture
• Fibrous
  
  • elongated and generally soluablee

Question 4

What are the domain fold classes?

Answer 4

Question 5

How do we identify similarity in protein structure?

Answer 5

• superpose the structures, often just the C alpha atoms, and quantify on average the separation between equivalent positions
• quantified as root mean square deviation of equivalenced position
• Often need to introduce gaps
• Quuote RMS for number of atoms superposed out of how many
• RMS depends on number equivalenced

Question 6

Conservation and variation in homologous proteins

Answer 6

Question 7

Functional conservation and EC nomenclature

Answer 7

• the 4 digit EC nomenclature provides tool 3 difit code
  
  • all 4 digits the same - same reaction on same substrate
  • 3 digit the same - same reaction but different substrates
  • <3 digits the same - quite different reactions

Question 8

What car the EC codes for different classes of anzxymes?

Answer 8

Question 9

How common is convergence of function?

Answer 9

• • About 15% of enzyme active sites occur more than
    once (i.e. mechanistic analogues)
• • NB Sometimes one sees side-chains with similar
    chemical properties (e.g. Asp in one enzyme and Glu
    in another)

Question 10

Convergence of fold

Answer 10

• some folds found very often between proteins with veery different functioons
• suggest favourable energetic arrangement and proteins have converged to somilar fold
• • e.g. 4-α helical bundle , TIM (β/α)8 barrel
• • But difficult to distinguish convergence and
    divergence

Question 11

What is a superfamily?

Answer 11

• a set of proteins that have all evolved directly from a common ancestor
• May have similar consequences that can be detected computationally but sometimes sequence similarity too remote to be detected
• may or may not have similar function

Question 12

Scop Hierarchical classification

Answer 12

Question 13

SCOP Topology

Answer 13

• domaisn classified in the same overall fold
  
  • more or less the same secondary structure elements
  • the same or siimilar connection topology
  • sometimes with differing loop structures

SCOP families are manually constructed

A closer evolutionary relationship between proteins
Often similar function
Higher level of sequence identity (often >35% but not fixed)

Question 14

CATH domain classification

Answer 14