2LDJ

1H Chemical Shift Assignments and structure of Trp-Cage mini-protein with D-amino acid

Summary for 2LDJ

• Entry DOI: 10.2210/pdb2ldj/pdb
• NMR Information: BMRB: 17669
• Descriptor: Trp-Cage mini-protein (1 entity in total)
• Functional Keywords: computational protein design, d-amino acid, de novo protein
• Total number of polymer chains: 1
• Total formula weight: 2242.49

Authors

Granillo, A.R.,Annavarapu, S.,Zhang, L.,Koder, R.,Nanda, V. (deposition date: 2011-05-27, release date: 2011-11-23, Last modification date: 2024-10-30)

Primary citation

Rodriguez-Granillo, A.,Annavarapu, S.,Zhang, L.,Koder, R.L.,Nanda, V.
Computational Design of Thermostabilizing d-Amino Acid Substitutions.
J.Am.Chem.Soc., 133:18750-18759, 2011

PubMed Abstract: Judicious incorporation of D-amino acids in engineered proteins confers many advantages such as preventing degradation by endogenous proteases and promoting novel structures and functions not accessible to homochiral polypeptides. Glycine to D-alanine substitutions at the carboxy termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by D-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using D-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing D-amino acid mutations. Substituting a key glycine in the Trp-cage miniprotein with D-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces both at the α-helix C-terminus and throughout the protein.

PubMed: 21978298
DOI: 10.1021/ja205609c

Experimental method

SOLUTION NMR