Home » Biosciences » Biochemistry » Lesk: Introduction to Genomics » Student resources » Rotating figures » Chapter 04
Lesk: Introduction to Genomics
Chapter 04
Please note: the filesize of some of the rotating structures is over 1MB and they may take a moment to view
Page 230, Fig 4.13
Factor XIIIa is the enzyme at the final step of the blood coagulation cascade. It cross-links fibrin molecules, stabilizing clots. The normal protein contains an arginine sidechain that forms a salt bridge and multiple hydrogen bonds to a neighbouring asparate sidechain and to mainchain carbonyl atoms. The arginine and aspartate sidechains are shown in green.
Mutation of the arginine to an isoleucine (not shown) removes these interactions, destabilizing the protein and resulting in poor clot formation [1F13].
rotating [672KB];
static
Page 230, Fig 4.14
Aldolase A is an enzyme in the glycolytic pathway. It is an isozyme of aldolase B, the protein involved in hereditary fructose intolerance. Aldolase is normally a tetramer, stabilized by hydrogen bonds involving an aspartate residue at the intersubunit interface. Mutation of this aspartate to a glycine destabilizes the tetramer. Although this has no detectable effect on most cell types, red blood cells show weakened cell membranes, causing a congenital form of haemolytic anaemia [2ALD].
rotating [599KB];
static
Page 231, Fig 4.15
Retinol-binding protein transports vitamin A around the bloodstream, bound in a deep hydrophobic cavity within the protein. This figure shows a model of mutant 75Gly→Asp of
retinol-binding protein. Note that the model was built solely by inserting the sidechain, to observe the structural consequences. No attempt was made to try to predict the structural deformation produced. What the model shows is that there are steric and electrostatic incompatibilities between the sidechain of 75Asp and the ligand. This explains the observation of decreased affinity for retinol, producing vitamin A deficiency and night blindness.
rotating [1.42MB];
static
Page 246, Fig 4.24
Local and global superpositions of protein structures.
(a) Two β-hairpins from the antigen-binding site of an antibody. [1VFA, 2FBJ]. Only mainchain
atoms are shown. The 'stems' of the loops, parts of strands of β-sheet, superpose well (black and cyan regions, at bottom of picture). The connections have different lengths and conformations, and do not superpose well (red and blue regions, at top of picture). This is an example of a local well-fitting substructure. It involves only a small contiguous region of the chains.
rotating [525KB];
static;
(b) Superposition of regions with a folding pattern called the HeH (helix-extended loop-helix). Black: domain from RNA-binding domain of transcriptional terminator protein ρ (from E. coli) [1A62]. Red: domain from KU heterodimer (human) [1JEQ]. This figure shows a 'chain trace,' a
polygon in space connecting one point from each residue. The helices at either end of the chains superpose well. The extended regions between the helices do not. The sequence alignment induced by the structural superposition is this:
rotating [764KB];
static;