3VB8

Crystal Structure of Engineered Protein, Northeast Structural Genomics Consortium Target OR43

3VB8 の概要

• エントリーDOI: 10.2210/pdb3vb8/pdb
• 分子名称: Engineered protein, SULFATE ION (3 entities in total)
• 機能のキーワード: structural genomics, psi-biology, northeast structural genomics consortium, nesg, de novo protein
• 由来する生物種: artificial gene
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38539.87

構造登録者

Seetharaman, J.,Su, M.,Procko, E.,Baker, D.,Ciccosanti, C.,Sahdev, S.,Xiao, R.,Everett, J.K.,Acton, T.B.,Montelione, G.T.,Hunt, J.F.,Tong, L.,Northeast Structural Genomics Consortium (NESG) (登録日: 2011-12-31, 公開日: 2012-06-06, 最終更新日: 2023-09-13)

主引用文献

Procko, E.,Hedman, R.,Hamilton, K.,Seetharaman, J.,Fleishman, S.J.,Su, M.,Aramini, J.,Kornhaber, G.,Hunt, J.F.,Tong, L.,Montelione, G.T.,Baker, D.
Computational design of a protein-based enzyme inhibitor.
J.Mol.Biol., 425:3563-3575, 2013

PubMed Abstract: While there has been considerable progress in designing protein-protein interactions, the design of proteins that bind polar surfaces is an unmet challenge. We describe the computational design of a protein that binds the acidic active site of hen egg lysozyme and inhibits the enzyme. The design process starts with two polar amino acids that fit deep into the enzyme active site, identifies a protein scaffold that supports these residues and is complementary in shape to the lysozyme active-site region, and finally optimizes the surrounding contact surface for high-affinity binding. Following affinity maturation, a protein designed using this method bound lysozyme with low nanomolar affinity, and a combination of NMR studies, crystallography, and knockout mutagenesis confirmed the designed binding surface and orientation. Saturation mutagenesis with selection and deep sequencing demonstrated that specific designed interactions extending well beyond the centrally grafted polar residues are critical for high-affinity binding.

PubMed: 23827138
DOI: 10.1016/j.jmb.2013.06.035

実験手法

X-RAY DIFFRACTION (2.9 Å)