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Prehistory
• Ph.D. with Peter Pauling, at University College London. ‘The crystal structures of some molecules active at cholinergic nerve receptors’, 1973
• Post-doc at LMB with David Blow• Collaborations with Fred Richards
(Yale), Michael Levitt (Weizmann Institute of Science), Joël Janin (Institut Pasteur, Paris)
• Return to England in 1976 …
220 – 175 + 1 = 46
270 – 225 + 1 = 46
46 + 46 = 92
Sperm whale myoglobin (yellow)
Lupin leghaemoglobin (red)
Importance of helix-helix contacts as determinants of structure
· Residue packing at helix interfaces produces discrete geometries of interhelical angles
Poplar leaf plastocyanin Alcaligenes denitrificans azurin
Insulin4-Zn form
Courtesy Nature Publishing Group
Insulin4-Zn form
Complete IgG [1IGT]
Six antigen-binding loops, or complementarity-determining regions (CDRs)
The canonical-structure model
· Five of the six antigen-binding loops – L1, L2, L3, H1 and H2, but NOT H3 – have individual discrete, small conformational repertoires, a set of canonical structures.
· The conformation can in most cases be predicted from sequence signatures.
Glycolate oxidase, a ‘TIM barrel’
‘Roll out the barrel’
• Number of strands (n) and shear number (S) define geometry of β-barrels.
• Simple if S/n integral – then residues segregate into layers
• ‘Periodic table’ of β-barrels based on S and n
• (For serine proteinases, n = 6 and S = 8; 8/6 is NOT integral; what happens is quite an interesting story.)
‘TIM barrel’
Final comment :
I have another sabbatical coming up …