6D37

Trp-cage tr16b R16Nva : Elimination of pH Dependent Interactions

Summary for 6D37

• Entry DOI: 10.2210/pdb6d37/pdb
• NMR Information: BMRB: 30453
• Descriptor: ALA-TYR-ALA-GLN-TRP-LEU-ALA-ASP-DAL-GLY-PRO-ALA-SER-DAL-NVA-PRO-PRO-PRO-SER (1 entity in total)
• Functional Keywords: miniprotein, de novo protein, trp-cage, circular permutant, microprotein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 1893.08

Authors

Byrne, A.,Andersen, N.H. (deposition date: 2018-04-14, release date: 2019-03-13, Last modification date: 2024-10-16)

Primary citation

Graham, K.A.,Byrne, A.,Son, R.,Andersen, N.H.
Reversing the typical pH stability profile of the Trp-cage.
Biopolymers, 110:e23260-e23260, 2019

PubMed Abstract: The Trp-cage, an 18-20 residue miniprotein, has emerged as a primary test system for evaluating computational fold prediction and folding rate determination efforts. As it turns out, a number of stabilizing interactions in the Trp-cage folded state have a strong pH dependence; all prior Trp-cage mutants have been destabilized under carboxylate-protonating conditions. Notable among the pH dependent stabilizing interactions within the Trp-cage are: (1) an Asp as the helix N-cap, (2) an H-bonded Asp9/Arg16 salt bridge, (3) an interaction between the chain termini which are in close spatial proximity, and (4) additional side chain interactions with Asp9. In the present study, we have prepared Trp-cage species that are significantly more stable at pH 2.5 (rather than 7) and quantitated the contribution of each interaction listed above. The Trp-cage structure remains constant with the pH change. The study has also provided measures of the stabilizing contribution of indole ring shielding from surface exposure and the destabilizing effects of an ionized Asp at the C-terminus of an α-helix.

PubMed: 30779444
DOI: 10.1002/bip.23260

Experimental method

SOLUTION NMR