1KMA

NMR Structure of the Domain-I of the Kazal-type Thrombin Inhibitor Dipetalin

1KMA の概要

• エントリーDOI: 10.2210/pdb1kma/pdb
• NMR情報: BMRB: 5276
• 分子名称: DIPETALIN (1 entity in total)
• 機能のキーワード: disulphide-rich small alpha+beta fold, kazal-type, blood clotting
• 由来する生物種: Dipetalogaster maximus
• 細胞内の位置: Secreted: O96790
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6090.67

構造登録者

Schlott, B.,Wohnert, J.,Icke, C.,Hartmann, M.,Ramachandran, R.,Guhrs, K.-H.,Glusa, E.,Flemming, J.,Gorlach, M.,Grosse, F.,Ohlenschlager, O. (登録日: 2001-12-14, 公開日: 2002-05-15, 最終更新日: 2024-10-16)

主引用文献

Schlott, B.,Wohnert, J.,Icke, C.,Hartmann, M.,Ramachandran, R.,Guhrs, K.H.,Glusa, E.,Flemming, J.,Gorlach, M.,Grosse, F.,Ohlenschlager, O.
Interaction of Kazal-type inhibitor domains with serine proteinases: biochemical and structural studies.
J.Mol.Biol., 318:533-546, 2002

PubMed Abstract: The interaction of domains of the Kazal-type inhibitor protein dipetalin with the serine proteinases thrombin and trypsin is studied. The functional studies of the recombinantly expressed domains (Dip-I+II, Dip-I and Dip-II) allow the dissection of the thrombin inhibitory properties and the identification of Dip-I as a key contributor to thrombin/dipetalin complex stability and its inhibitory potency. Furthermore, Dip-I, but not Dip-II, forms a complex with trypsin resulting in an inhibition of the trypsin activity directed towards protein substrates. The high resolution NMR structure of the Dip-I domain is determined using multi-dimensional heteronuclear NMR spectroscopy. Dip-I exhibits the canonical Kazal-type fold with a central alpha-helix and a short two-stranded antiparallel beta-sheet. Molecular regions essential for inhibitor complex formation with thrombin and trypsin are identified. A comparison with molecular complexes of other Kazal-type thrombin and trypsin inhibitors by molecular modeling shows that the N-terminal segment of Dip-I fulfills the structural prerequisites for inhibitory interactions with either proteinase and explains the capacity of this single Kazal-type domain to interact with different proteinases.

PubMed: 12051857
DOI: 10.1016/S0022-2836(02)00014-1

実験手法

SOLUTION NMR