1MH5

The Structure Of The Complex Of The Fab Fragment Of The Esterolytic Antibody MS6-164 and A Transition-State Analog

1MH5 の概要

• エントリーDOI: 10.2210/pdb1mh5/pdb
• 関連するPDBエントリー: 1MIE 1MJ7 1MJ8 1MJJ 1MJU
• 分子名称: IMMUNOGLOBULIN MS6-164, SULFATE ION, N-{[2-({[1-(4-CARBOXYBUTANOYL)AMINO]-2-PHENYLETHYL}-HYDROXYPHOSPHINYL)OXY]ACETYL}-2-PHENYLETHYLAMINE, ... (5 entities in total)
• 機能のキーワード: catalytic antibody, ester hydrolysis, esterolytic, fab, immunoglobulin, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 99216.72

構造登録者

Ruzheinikov, S.N.,Muranova, T.A.,Sedelnikova, S.E.,Partridge, L.J.,Blackburn, G.M.,Murray, I.A.,Kakinuma, H.,Takashi, N.,Shimazaki, K.,Sun, J.,Nishi, Y.,Rice, D.W. (登録日: 2002-08-19, 公開日: 2003-09-23, 最終更新日: 2024-10-30)

主引用文献

Ruzheinikov, S.N.,Muranova, T.A.,Sedelnikova, S.E.,Partridge, L.J.,Blackburn, G.M.,Murray, I.A.,Kakinuma, H.,Takashi, N.,Shimazaki, K.,Sun, J.,Nishi, Y.,Rice, D.W.
High-resolution crystal structure of the Fab-fragments of a family of mouse catalytic antibodies with esterase activity
J.Mol.Biol., 332:423-435, 2003

PubMed Abstract: The crystal structures of four related Fab fragments of a family of catalytic antibodies displaying differential levels of esterase activity have been solved in the presence and in the absence of the transition-state analogue (TSA) that was used to elicit the immune response. The electron density maps show that the TSA conformation is essentially identical, with limited changes on hapten binding. Interactions with the TSA explain the specificity for the D rather than the L-isomer of the substrate. Differences in the residues in the hapten-binding pocket, which increase hydrophobicity, appear to correlate with an increase in the affinity of the antibodies for their substrate. Analysis of the structures at the active site reveals a network of conserved hydrogen bond contacts between the TSA and the antibodies, and points to a critical role of two conserved residues, HisL91 and LysH95, in catalysis. However, these two key residues are set into very different contexts in their respective structures, with an apparent direct correlation between the catalytic power of the antibodies and the complexity of their interactions with the rest of the protein. This suggests that the catalytic efficiency may be controlled by contacts arising from a second sphere of residues at the periphery of the active site.

PubMed: 12948492
DOI: 10.1016/S0022-2836(03)00902-1

実験手法

X-RAY DIFFRACTION (2.1 Å)