3U3B

Crystal Structure of Computationally Redesigned Four-Helix Bundle

Summary for 3U3B

• Entry DOI: 10.2210/pdb3u3b/pdb
• Related: 1TQG 2LCH
• Descriptor: computationally designed four-helix bundle protein (2 entities in total)
• Functional Keywords: four-helix bundle, flexible backbone protein design, hyperthermostable, unknown function
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 26532.90

Authors

Murphy, G.S.,Machius, M. (deposition date: 2011-10-05, release date: 2012-06-13, Last modification date: 2024-04-03)

Primary citation

Murphy, G.S.,Mills, J.L.,Miley, M.J.,Machius, M.,Szyperski, T.,Kuhlman, B.
Increasing sequence diversity with flexible backbone protein design: the complete redesign of a protein hydrophobic core.
Structure, 20:1086-1096, 2012

PubMed Abstract: Protein design tests our understanding of protein stability and structure. Successful design methods should allow the exploration of sequence space not found in nature. However, when redesigning naturally occurring protein structures, most fixed backbone design algorithms return amino acid sequences that share strong sequence identity with wild-type sequences, especially in the protein core. This behavior places a restriction on functional space that can be explored and is not consistent with observations from nature, where sequences of low identity have similar structures. Here, we allow backbone flexibility during design to mutate every position in the core (38 residues) of a four-helix bundle protein. Only small perturbations to the backbone, 1-2 Å, were needed to entirely mutate the core. The redesigned protein, DRNN, is exceptionally stable (melting point >140°C). An NMR and X-ray crystal structure show that the side chains and backbone were accurately modeled (all-atom RMSD = 1.3 Å).

PubMed: 22632833
DOI: 10.1016/j.str.2012.03.026

Experimental method

X-RAY DIFFRACTION (1.854 Å)