1GB4

HYPERTHERMOPHILIC VARIANT OF THE B1 DOMAIN FROM STREPTOCOCCAL PROTEIN G, NMR, 47 STRUCTURES

Summary for 1GB4

• Entry DOI: 10.2210/pdb1gb4/pdb
• Descriptor: GB1-C3B4 (1 entity in total)
• Functional Keywords: hyperthermophile, streptococcal protein g
• Biological source: Streptococcus sp.
• Total number of polymer chains: 1
• Total formula weight: 6367.06

Authors

Malakauskas, S.M.,Mayo, S.L. (deposition date: 1998-01-19, release date: 1998-07-22, Last modification date: 2024-05-22)

Primary citation

Malakauskas, S.M.,Mayo, S.L.
Design, structure and stability of a hyperthermophilic protein variant.
Nat.Struct.Biol., 5:470-475, 1998

PubMed Abstract: Here we report the use of an objective computer algorithm in the design of a hyperstable variant of the Streptococcal protein Gbeta1 domain (Gbeta1). The designed seven-fold mutant, Gbeta1-c3b4, has a melting temperature in excess of 100 degrees C and an enhancement in thermodynamic stability of 4.3 kcal mol(-1) at 50 degrees C over the wild-type protein. Gbeta1-c3b4 maintains the Gbeta1 fold, as determined by nuclear magnetic resonance spectroscopy, and also retains a significant level of binding to human IgG in qualitative comparisons with wild type. The basis of the stability enhancement appears to have multiple components including optimized core packing, increased burial of hydrophobic surface area, more favorable helix dipole interactions, and improvement of secondary structure propensity. The design algorithm is able to model such complex contributions simultaneously using empirical physical/chemical potential functions and a combinatorial optimization algorithm based on the dead-end elimination theorem. Because the design methodology is based on general principles, there is the potential of applying the methodology to the stabilization of other unrelated protein folds.

PubMed: 9628485
DOI: 10.1038/nsb0698-470

Experimental method

SOLUTION NMR