PDBsum entry 3b83

Unknown function

PDB id

3b83

Contents

			Protein chains

					(+ 2 more) 95 a.a.

			Waters ×47

References listed in PDB file

Key reference

Title

Computer-Based redesign of a beta sandwich protein suggests that extensive negative design is not required for de novo beta sheet design.

Authors

X.Hu, H.Wang, H.Ke, B.Kuhlman.

Ref.

Structure, 2008, 16, 1799-1805. [DOI no: 10.1016/j.str.2008.09.013]

PubMed id

19081056

Abstract

The de novo design of globular beta sheet proteins remains largely an unsolved problem. It is unclear whether most designs are failing because the designed sequences do not have favorable energies in the target conformations or whether more emphasis should be placed on negative design, that is, explicitly identifying sequences that have poor energies when adopting undesired conformations. We tested whether we could redesign the sequence of a naturally occurring beta sheet protein, tenascin, with a design algorithm that does not include explicit negative design. Denaturation experiments indicate that the designs are significantly more stable than the wild-type protein and the crystal structure of one design closely matches the design model. These results suggest that extensive negative design is not required to create well-folded beta sandwich proteins. However, it is important to note that negative design elements may be encoded in the conformation of the protein backbone which was preserved from the wild-type protein.



	Figure 1. Figure 1. Sequences of the Wild-Type and Three Redesigned Proteins TEN-WT, wild-type; TEN-D1, TEN-D2, and TEN-D3, redesigned sequences. The TEN-D1 sequence is from a previously published study (Dantas et al., 2003).		Figure 5. Figure 5. Structure Alignment between the Designed Model and the Crystal Structure of TEN-D3 Designed model, cyan; TEN-D3, green. (A) Backbone only. (B) Buried residues. (C) Selected surface residues. (D) A designed salt bridge between Asp48 and Arg74.

PROCHECK

	Headers