1QMN

Alpha1-antichymotrypsin serpin in the delta conformation (partial loop insertion)

1QMN の概要

• エントリーDOI: 10.2210/pdb1qmn/pdb
• 関連するPDBエントリー: 1AS4 2ACH 3CAA 4CAA
• 分子名称: ALPHA-1-ANTICHYMOTRYPSIN (1 entity in total)
• 機能のキーワード: serpin, serine proteinase inhibitor, hydrolase inhibitor loop-sheet polymerization, emphysema, disease mutation, acute phase protein, conformational disease, hydrolase inhibitor
• 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: 45353.69

構造登録者

Gooptu, B.,Hazes, B.,Lomas, D.A. (登録日: 1999-10-04, 公開日: 2000-01-17, 最終更新日: 2023-12-13)

主引用文献

Gooptu, B.,Hazes, B.,Chang, W.-S.W.,Dafforn, T.R.,Carrell, R.W.,Read, R.J.,Lomas, D.A.
Inactive Conformation of the Serpin Alpha1-Antichymotrypsin Indicates Two-Stage Insertion of the Reactive Loop: Implications for Inhibitory Function and Conformational Disease
Proc.Natl.Acad.Sci.USA, 97:67-, 2000

PubMed Abstract: The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into beta-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by beta-strand exchange between the reactive loop of one molecule and beta-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55-Pro) of the plasma serpin alpha(1)-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into beta-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma alpha(1)-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55-Pro mutation.

PubMed: 10618372
DOI: 10.1073/PNAS.97.1.67

実験手法

X-RAY DIFFRACTION (2.27 Å)