8F9O

Dog sialic acid esterase (SIAE)

8F9O の概要

• エントリーDOI: 10.2210/pdb8f9o/pdb
• 分子名称: Sialic acid acetylesterase, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: sialic acid, sialate o-acetylesterase, hydrolase
• 由来する生物種: Canis lupus familiaris (dog)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 59211.39

構造登録者

Ide, D.,Gorelik, A.,Illes, K.,Nagar, B. (登録日: 2022-11-24, 公開日: 2024-05-29, 最終更新日: 2024-10-23)

主引用文献

Ide, D.,Gorelik, A.,Illes, K.,Nagar, B.
Structural Analysis of Mammalian Sialic Acid Esterase.
J.Mol.Biol., 436:168801-168801, 2024

PubMed Abstract: Sialic acid esterase (SIAE) catalyzes the removal of O-acetyl groups from sialic acids found on cell surface glycoproteins to regulate cellular processes such as B cell receptor signalling and apoptosis. Loss-of-function mutations in SIAE are associated with several common autoimmune diseases including Crohn's, ulcerative colitis, and arthritis. To gain a better understanding of the function and regulation of this protein, we determined crystal structures of SIAE from three mammalian homologs, including an acetate bound structure. The structures reveal that the catalytic domain adopts the fold of the SGNH hydrolase superfamily. The active site is composed of a catalytic dyad, as opposed to the previously reported catalytic triad. Attempts to determine a substrate-bound structure yielded only the hydrolyzed product acetate in the active site. Rigid docking of complete substrates followed by molecular dynamics simulations revealed that the active site does not form specific interactions with substrates, rather it appears to be broadly specific to accept sialoglycans with diverse modifications. Based on the acetate bound structure, a catalytic mechanism is proposed. Structural mapping of disease mutations reveals that most are located on the surface of the enzyme and would only cause minor disruptions to the protein fold, suggesting that these mutations likely affect binding to other factors. These results improve our understanding of SIAE biology and may aid in the development of therapies for autoimmune diseases and cancer.

PubMed: 39321866
DOI: 10.1016/j.jmb.2024.168801

実験手法

X-RAY DIFFRACTION (1.25 Å)