2EVQ

Solution structure of HP7, a 12-residue beta hairpin

Summary for 2EVQ

• Entry DOI: 10.2210/pdb2evq/pdb
• Descriptor: HP7 (1 entity in total)
• Functional Keywords: beta hairpin, trp/trp packing, de novo protein
• Total number of polymer chains: 1
• Total formula weight: 1420.57

Authors

Andersen, N.H.,Olsen, K.A.,Fesinmeyer, R.M. (deposition date: 2005-10-31, release date: 2006-03-07, Last modification date: 2024-05-22)

Primary citation

Andersen, N.H.,Olsen, K.A.,Fesinmeyer, R.M.,Tan, X.,Hudson, F.M.,Eidenschink, L.A.,Farazi, S.R.
Minimization and Optimization of Designed beta-Hairpin Folds
J.Am.Chem.Soc., 128:6101-6110, 2006

PubMed Abstract: Minimized beta hairpins have provided additional data on the geometric preferences of Trp interactions in TW-loop-WT motifs. This motif imparts significant fold stability to peptides as short as 8 residues. High-resolution NMR structures of a 16- (KKWTWNPATGKWTWQE, DeltaG(U)(298) >or= +7 kJ/mol) and 12-residue (KTWNPATGKWTE, DeltaG(U)(298) = +5.05 kJ/mol) hairpin reveal a common turn geometry and edge-to-face (EtF) packing motif and a cation-pi interaction between Lys(1) and the Trp residue nearest the C-terminus. The magnitude of a CD exciton couplet (due to the two Trp residues) and the chemical shifts of a Trp Hepsilon3 site (shifted upfield by 2.4 ppm due to the EtF stacking geometry) provided near-identical measures of folding. CD melts of representative peptides with the -TW-loop-WT- motif provided the thermodynamic parameters for folding, which reflect enthalpically driven folding at laboratory temperatures with a small DeltaC(p) for unfolding (+420 J K(-)(1)/mol). In the case of Asx-Pro-Xaa-Thr-Gly-Xaa loops, mutations established that the two most important residues in this class of direction-reversing loops are Asx and Gly: mutation to alanine is destabilizing by about 6 and 2 kJ/mol, respectively. All indicators of structuring are retained in a minimized 8-residue construct (Ac-WNPATGKW-NH(2)) with the fold stability reduced to DeltaG(U)(278) = -0.7 kJ/mol. NMR and CD comparisons indicate that -TWXNGKWT- (X = S, I) sequences also form the same hairpin-stabilizing W/W interaction.

PubMed: 16669679
DOI: 10.1021/ja054971w

Experimental method

SOLUTION NMR