1AAP

X-RAY CRYSTAL STRUCTURE OF THE PROTEASE INHIBITOR DOMAIN OF ALZHEIMER'S AMYLOID BETA-PROTEIN PRECURSOR

1AAP の概要

• エントリーDOI: 10.2210/pdb1aap/pdb
• 分子名称: ALZHEIMER'S DISEASE AMYLOID A4 PROTEIN (2 entities in total)
• 機能のキーワード: proteinase inhibitor (trypsin)
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12840.29

構造登録者

Hynes, T.R.,Randal, M.,Kennedy, L.A.,Eigenbrot, C.,Kossiakoff, A.A. (登録日: 1990-09-14, 公開日: 1991-10-15, 最終更新日: 2024-10-30)

主引用文献

Hynes, T.R.,Randal, M.,Kennedy, L.A.,Eigenbrot, C.,Kossiakoff, A.A.
X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor.
Biochemistry, 29:10018-10022, 1990

PubMed Abstract: Alzheimer's amyloid beta-protein precursor contains a Kunitz protease inhibitor domain (APPI) potentially involved in proteolytic events leading to cerebral amyloid deposition. To facilitate the identification of the physiological target of the inhibitor, the crystal structure of APPI has been determined and refined to 1.5-A resolution. Sequences in the inhibitor-protease interface of the correct protease target will reflect the molecular details of the APPI structure. While the overall tertiary fold of APPI is very similar to that of the Kunitz inhibitor BPTI, a significant rearrangement occurs in the backbone conformation of one of the two protease binding loops. A number of Kunitz inhibitors have similar loop sequences, indicating the structural alteration is conserved and potentially an important determinant of inhibitor specificity. In a separate region of the protease binding loops, APPI side chains Met-17 and Phe-34 create an exposed hydrophobic surface in place of Arg-17 and Val-34 in BPTI. The restriction this change places on protease target sequences is seen when the structure of APPI is superimposed on BPTI complexed to serine proteases, where the hydrophobic surface of APPI faces a complementary group of nonpolar side chains on kallikrein A versus polar side chains on trypsin.

PubMed: 2125487
DOI: 10.1021/bi00495a002

実験手法

X-RAY DIFFRACTION (1.5 Å)