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Neutron and X-ray crystallographic analysis of the human α-thrombin-bivalirudin complex at pD 5.0: protonation states and hydration structure of the enzyme-product complex.

Yamada T, Kurihara K, Ohnishi Y, Tamada T, Tomoyori K, Masumi K, Tanaka I, Kuroki R, Niimura N
Biochim Biophys Acta 1834 1532-8 (2013)
Cited: 5 times
EuropePMC logo PMID: 23712263

Abstract

The protonation states and hydration structures of the α-thrombin-bivalirudin complex were studied by joint XN refinement of the single crystal X-ray and neutron diffraction data at resolutions of 1.6 and 2.8Å, respectively. The atomic distances were estimated by carrying out X-ray crystallographic analysis at 1.25Å resolution. The complex represents a model of the enzyme-product (EP) complex of α-thrombin. The neutron scattering length maps around the active site suggest that the side chain of H57/H was deuterated. The joint XN refinement showed that occupancies for Dδ1 and Dε2 of H57/H were 1.0 and 0.7, respectively. However, no significant neutron scattering length density was observed around the hydroxyl oxygen Oγ of S195/H, which was close to the carboxylic carbon atom of dFPR-COOH. These observations suggest that the Oγ atom of S195/H is deprotonated and maintains its nucleophilicity in the EP complex. In addition to the active site, the hydration structures of the S1 subsite and the Exosite I, which are involved in the recognition of bivalirudin, are presented.

Reviews - 3vxe mentioned but not cited (2)

  1. Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands. Troisi R, Balasco N, Autiero I, Vitagliano L, Sica F. Int J Mol Sci 22 10803 (2021)
  2. Capturing the geometry, function, and evolution of enzymes with 3D templates. Riziotis IG, Thornton JM. Protein Sci 31 e4363 (2022)


Reviews citing this publication (2)

  1. Neutron protein crystallography: A complementary tool for locating hydrogens in proteins. O'Dell WB, Bodenheimer AM, Meilleur F. Arch Biochem Biophys 602 48-60 (2016)
  2. Peptide hormones and lipopeptides: from self-assembly to therapeutic applications. Hutchinson JA, Burholt S, Hamley IW. J Pept Sci 23 82-94 (2017)

Articles citing this publication (1)

  1. New insight into the traditional model of the coagulation cascade and its regulation: illustrated review of a three-dimensional view. Troisi R, Balasco N, Autiero I, Sica F, Vitagliano L. Res Pract Thromb Haemost 7 102160 (2023)


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