3BF6

Thrombin:suramin complex

3BF6 の概要

• エントリーDOI: 10.2210/pdb3bf6/pdb
• 関連するPDBエントリー: 1PPB 2H9T
• 分子名称: Thrombin, LIGHT CHAIN, Thrombin, HEAVY CHAIN, PHE-PRO-ARG, ... (5 entities in total)
• 機能のキーワード: thrombin, suramin, blood, coagulation, acute phase, blood coagulation, cleavage on pair of basic residues, disease mutation, gamma-carboxyglutamic acid, glycoprotein, hydrolase, kringle, protease, secreted, serine protease, zymogen
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space: P00734 P00734
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 35593.53

構造登録者

Lima, L.M.T.R.,Polikarpov, I.,Monteiro, R.Q. (登録日: 2007-11-20, 公開日: 2007-12-25, 最終更新日: 2024-11-20)

主引用文献

Lima, L.M.,Becker, C.F.,Giesel, G.M.,Marques, A.F.,Cargnelutti, M.T.,de Oliveira Neto, M.,Queiroz Monteiro, R.,Verli, H.,Polikarpov, I.
Structural and thermodynamic analysis of thrombin:suramin interaction in solution and crystal phases.
Biochim.Biophys.Acta, 1794:873-881, 2009

PubMed Abstract: Suramin is a hexasulfonated naphthylurea which has been recently characterized as a non-competitive inhibitor of human alpha-thrombin activity over fibrinogen, although its binding site and mode of interaction with the enzyme remain elusive. Here, we determined two X-ray structure of the thrombin:suramin complex, refined at 2.4 A resolution. While a single thrombin:suramin complex was found in the asymmetric unit cell of the crystal, some of the crystallographic contacts with symmetrically related molecules are mediated by both the enzyme and the ligand. Molecular dynamics simulations with the 1:1 complex demonstrate a large rearrangement of suramin in the complex, but with the protein scaffold and the more extensive protein-ligand regions keep unchanged. Small-angle X-ray scattering measurements at high micromolar concentration demonstrate a suramin-induced dimerization of the enzyme. These data indicating a dissimilar binding mode in the monomeric and oligomeric states, with a monomeric, 1:1 complex to be more likely to exist at the thrombin physiological, nanomolar concentration range. Collectively, close understanding on the structural basis for interaction is given which might establish a basis for design of suramin analogues targeting thrombin.

PubMed: 19332154
DOI: 10.1016/j.bbapap.2009.03.011

実験手法

X-RAY DIFFRACTION (2.5 Å)