2YD0

Crystal structure of the soluble domain of human endoplasmic reticulum aminopeptidase 1 ERAP1

「2XDT」から置き換えられました

2YD0 の概要

• エントリーDOI: 10.2210/pdb2yd0/pdb
• 分子名称: ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: hydrolase, glycoprotein, metal-binding, metalloprotease, protease, adaptive immunity
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 104180.06

構造登録者

Vollmar, M.,Kochan, G.,Krojer, T.,Ugochukwu, E.,Muniz, J.R.C.,Raynor, J.,Chaikuad, A.,Allerston, C.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Weigelt, J.,Edwards, A.,Knapp, S. (登録日: 2011-03-17, 公開日: 2011-04-13, 最終更新日: 2024-10-23)

主引用文献

Kochan, G.,Krojer, T.,Harvey, D.,Fischer, R.,Chen, L.,Vollmar, M.,von Delft, F.,Kavanagh, K.L.,Brown, M.A.,Bowness, P.,Wordsworth, P.,Kessler, B.M.,Oppermann, U.
Crystal Structures of the Endoplasmic Reticulum Aminopeptidase-1 (Erap1) Reveal the Molecular Basis for N-Terminal Peptide Trimming.
Proc.Natl.Acad.Sci.USA, 108:7745-, 2011

PubMed Abstract: Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-(X)(18)-E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K(528)R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.

PubMed: 21508329
DOI: 10.1073/PNAS.1101262108

実験手法

X-RAY DIFFRACTION (2.7 Å)