3H09

The structure of Haemophilus influenzae IgA1 protease

3H09 の概要

• エントリーDOI: 10.2210/pdb3h09/pdb
• 分子名称: Immunoglobulin A1 protease, ACETATE ION, MALONIC ACID, ... (5 entities in total)
• 機能のキーワード: serine protease, immunoglobulin a1, beta helix, hydrolase, membrane, protease, secreted, transmembrane, virulence, zymogen
• 由来する生物種: Haemophilus influenzae
• 細胞内の位置: Immunoglobulin A1 protease autotransporter: Periplasm . Immunoglobulin A1 protease: Secreted. Immunoglobulin A1 protease translocator: Cell outer membrane ; Multi-pass membrane protein : P44969
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 218453.11

構造登録者

Johnson, T.A.,Qiu, J.,Plaut, A.G.,Holyoak, T. (登録日: 2009-04-08, 公開日: 2009-04-21, 最終更新日: 2023-09-06)

主引用文献

Johnson, T.A.,Qiu, J.,Plaut, A.G.,Holyoak, T.
Active-Site Gating Regulates Substrate Selectivity in a Chymotrypsin-Like Serine Protease The Structure of Haemophilus influenzae Immunoglobulin A1 Protease.
J.Mol.Biol., 389:559-574, 2009

PubMed Abstract: We report here the first structure of a member of the immunoglobulin A protease (IgAP) family at 1.75-A resolution. This protease is a founding member of the type V (autotransporter) secretion system and is considered a virulence determinant among the bacteria expressing the enzyme. The structure of the enzyme fits that of a classic autotransporter in which several unique domains necessary for protein function are appended to a central, 100-A-long beta-helical domain. The N-terminal domain of the IgAP is found to possess a chymotrypsin-like fold. However, this catalytic domain contains a unique loop D that extends over the active site acting as a lid, gating substrate access. The data presented provide a structural basis for the known ability of IgAPs to cleave only the proline/serine/threonine-rich hinge peptide unique to IgA1 (isotype 1) in the context of the intact fold of the immunoglobulin. Based upon the structural data, as well as molecular modeling, a model suggesting that the unique extended loop D in this IgAP sterically occludes the active-site binding cleft in the absence of immunoglobulin binding is presented. Only in the context of binding of the IgA1-Fc domain in a valley formed between the N-terminal protease domain and another domain appended to the beta-helix spine (domain 2) is the lid stabilized in an open conformation. The stabilization of this open conformation through Fc association subsequently allows access of the hinge peptide to the active site, resulting in recognition and cleavage of the substrate.

PubMed: 19393662
DOI: 10.1016/j.jmb.2009.04.041

実験手法

X-RAY DIFFRACTION (1.75 Å)