Conformational features of a hexapeptide model Ac-TCAAKA-NH2 correspondingto a hydrated a helical segment from glyceraldehyde 3-phosphate dehydrogenase: Implications for the role of turns in helix folding

Recent analysis of alpha helices in protein crystal structures, available i n literature, revealed hydrated or helical segments in which, water molecul e breaks open helix 5-->1 hydrogen bond by inserting itself hydrogen bonds to both C=O and NH groups of helix hydrogen bond without disrupting the hel ix hydrogen bond, and hydrogen bonds to either C=O or NH of helix hydrogen bond. These hydrated segments display a variety of turn conformations and a n thought to be folding intermediates' trapped during folding-unfolding of alpha helices. A role for reverse turns is implicated ill the folding of al pha helices. We considered a hexapeptide model Ac-(1)TGAAKA(6)-NH2 from gly ceraldehyde 3-phosphate dehydrogenase, corresponding to a hydrated helical segment to assess its role in helix folding. The sequence is a site for two 'folding intermediates'. The conformational features of the model peptide have been investigated by H-1 2D NMR techniques and quantum mechanical. per turbative configuration interaction over localized orbitals (PCILO) method. Theoretical modeling largely correlates with experimental observations. Ba sed upon the amide proton temperature coefficients, the observed d alpha n( i, i+1), d alpha n(i, i+2), dnn(i, i+1), d beta n(i, i+1) NOEs and the resu lts from theoretical modeling, we conclude that the residues of the peptide sample alpha helical and neck regions of the Ramachandran phi, psi map wit h reduced conformational entropy and there is a potential for turn conforma tions at N and C terminal ends of the peptide. The role of reduced conforma tional entropy and turn potential in helix formation have been discussed. W e conclude that the peptide sequence can serve as a 'folding intermediate' in the helix folding of glyceraldehyde 3-phosphate dehydrogenase.