1FXY

COAGULATION FACTOR XA-TRYPSIN CHIMERA INHIBITED WITH D-PHE-PRO-ARG-CHLOROMETHYLKETONE

1FXY の概要

• エントリーDOI: 10.2210/pdb1fxy/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000020
• 分子名称: COAGULATION FACTOR XA-TRYPSIN CHIMERA, D-phenylalanyl-N-[(2S,3S)-6-{[amino(iminio)methyl]amino}-1-chloro-2-hydroxyhexan-3-yl]-L-prolinamide (3 entities in total)
• 機能のキーワード: chimera, protease, chloromethylketone, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space: P07477
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25122.80

構造登録者

Hopfner, K.P.,Kopetzki, E.,Kresse, G.-B.,Huber, R.,Bode, W.,Engh, R.A. (登録日: 1998-04-22, 公開日: 1998-06-17, 最終更新日: 2024-11-20)

主引用文献

Hopfner, K.P.,Kopetzki, E.,Kresse, G.B.,Bode, W.,Huber, R.,Engh, R.A.
New enzyme lineages by subdomain shuffling.
Proc.Natl.Acad.Sci.USA, 95:9813-9818, 1998

PubMed Abstract: Protein functions have evolved in part via domain recombination events. Such events, for example, recombine structurally independent functional domains and shuffle targeting, regulatory, and/or catalytic functions. Domain recombination, however, can generate new functions, as implied by the observation of catalytic sites at interfaces of distinct folding domains. If useful to an evolving organism, such initially rudimentary functions would likely acquire greater efficiency and diversity, whereas the initially distinct folding domains would likely develop into single functional domains. This represents the probable evolution of the S1 serine protease family, whose two homologous beta-barrel subdomains assemble to form the binding sites and the catalytic machinery. Among S1 family members, the contact interface and catalytic residues are highly conserved whereas surrounding surfaces are highly variable. This observation suggests a new strategy to engineer viable proteins with novel properties, by swapping folding subdomains chosen from among protein family members. Such hybrid proteins would retain properties conserved throughout the family, including folding stability as single domain proteins, while providing new surfaces amenable to directed evolution or engineering of specific new properties. We show here that recombining the N-terminal subdomain from coagulation factor X with the C-terminal subdomain from trypsin creates a potent enzyme (fXYa) with novel properties, in particular a broad substrate specificity. As shown by the 2.15-A crystal structure, plasticity at the hydrophobic subdomain interface maintains activity, while surface loops are displaced compared with the parent subdomains. fXYa thus represents a new serine proteinase lineage with hybrid fX, trypsin, and novel properties.

PubMed: 9707558
DOI: 10.1073/pnas.95.17.9813

実験手法

X-RAY DIFFRACTION (2.15 Å)