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SUMMARY:85 mutants\, 70 phi-values\, 4 years\, and one overdue PhD: - Adri
 an Nickson
DTSTART:20080227T103000Z
DTEND:20080227T113000Z
UID:TALK10511@talks.cam.ac.uk
CONTACT:Giorgio Favrin
DESCRIPTION:Protein-engineering methods (phi-values) were used to investig
 ate the folding transition state of a Lysin Motif (LysM) domain from Esche
 richia coli membrane-bound lytic murein transglycosylase D. This domain co
 nsists of just 48 structured residues in a symmetrical beta-alpha-alpha-be
 ta arrangement and is the smallest alpha/beta protein yet investigated usi
 ng these methods. An extensive mutational analysis revealed a highly robus
 t folding pathway with no detectable transition state plasticity\, indicat
 ing that LysM is an example of an ‘ideal’ two-state folder. The patter
 n of phi-values denotes a highly polarised transition state\, with signifi
 cant formation of the helices but no structure within the beta-sheet.\nRem
 arkably\, this transition state remains polarised after circularisation of
  the domain\, and exhibits an identical phi-value pattern\; however\, the 
 interactions within the transition state are uniformly weaker in the circu
 lar variant. This observation is supported by results from an Eyring analy
 sis of the folding rates of the two proteins\, and leads us to propose tha
 t the folding pathway of LysM is dominated by enthalpic rather than entrop
 ic considerations. We suggest that the lower entropy cost of formation of 
 the circular transition state is balanced\, to some extent\, by the lower 
 enthalpy of contacts within this structure. 
LOCATION:Todd Hamied Room\,  Department of Chemistry
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