X-Ray Structures

coverfigure2013

Consistent with the X-ray crystal structure and Luminescence Resonance Energy Transfer measurements of the distance between residues S101 and S210 (highlighted in red and pink, respectively), molecular dynamics calculations capture the transition between extended (top) and compact (bottom) conformations of prothrombin.

X-ray Structures:

  • 2THF, 1B7X, 1THP
    Unexpected crucial role of residue 225 in serine proteases. Guinto et al (1999) Proc Natl Acad Sci USA 96, 1852-1857.
  • 1MHO
    Crystal structure of the anticoagulant slow form of thrombin. Pineda et al (2002) J Biol Chem 277, 40177-40180.
  • 1SGI, 1SHH, 1SG8, 1SFQ
    Molecular dissection of Na+ binding to thrombin. Pineda et al (2004) J Biol Chem 279, 31842-31853.
  • 1TQ0, 1TQ7
    The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket. Pineda et al (2004) J Biol Chem 279, 39824-39828.
  • 1TWX
    Crystal structure of the thrombin mutant D221A/D222K: The Asp222:Arg187 ion-pair stabilizes the fast form. Pineda et al (2004) Biophys Chem 112, 253-256.
  • 1T31, 1T32
    A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo. de Garavilla et al (2005) J Biol Chem 280, 18001-18007.
  • 1Z8I, 1Z8J
    Energetic and structural consequences of perturbing Gly-193 in the oxyanion hole of serine proteases. Bobofchak et al (2005) J Biol Chem 280, 25644-25650.
  • 1Z8I, 1Z8J
    Energetic and structural consequences of perturbing Gly-193 in the oxyanion hole of serine proteases. Bobofchak et al (2005) J Biol Chem 280, 25644-25650.
  • 2A0Q
    Thrombin functions through its RGD sequence in a non-canonical conformation. Papaconstantinou et al (2005) J Biol Chem 280, 29393-29396.
  • 2A0Q
    High resolution crystal structures of free thrombin in the presence of K+ reveal the basis of monovalent cation selectivity and an inactive slow form. Carrell et al (2006) Biophys Chem 121, 177-184.
  • 2FMJ
    Conversion of trypsin into a Na+-activated enzyme. Page et al (2006) Biochemistry 45, 2987-2993.
  • 2GP9
    Crystal structure of thrombin in a self-inhibited conformation. Pineda et al (2006) J Biol Chem 281, 32922-32928.
  • 2HWL
    Crystal structure of thrombin in complex with fibrinogen gamma’ peptide. Pineda et al (2007) Biophys Chem 125, 556-559.
  • 2HVX
    Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. Greco et al (2007) J Med Chem 50, 1527-1530.
  • 2OCV, 2OD3
    Structural basis of Na+ activation mimicry in murine thrombin. Marino et al (2007) J Biol Chem 282, 16355-16361.
  • 2PUX, 2PV9
    Crystal structures of murine thrombin in complex with the extracellular fragments of protease-activated receptors PAR3 and PAR4. Bah et al (2007) Proc Natl Acad Sci USA 104, 11603-11608.
  • 2PGB, 2PGQ
    Important role of the Cys-191:Cys-220 disulfide bond in thrombin function and allostery. Bush-Pelc et al (2007) J Biol Chem 282, 27165-27170.
  • 3BEI, 3BEF
    Structural identification of the pathway of long-range communication in an allosteric enzyme. Gandhi et al (2008) Proc Natl Acad Sci USA 105, 1832-1837.
  • 3BEU
    Engineering protein allostery: 1.05 A resolution structure and enzymatic properties of a Na+-activated trypsin. Page et al (2008) J Mol Biol 378, 666-672.
  • 3BV9
    Thrombostatin FM compounds: direct thrombin inhibitors – mechanism of action in vitro and in vivo. Nieman et al (2008) J Thromb Haemost 6, 837-845.
  • 3E6P
    Na+ binding to meizothrombin desF1. Papaconstantinou et al (2008) Cell Mol Life Sci 65, 3688-3697.
  • 3GIC
    Stabilization of the E* form turns thrombin into an anticoagulant. Bah et al (2009) J Biol Chem 284, 20034-20040.
  • 3HK3, 3HK6, 3HKI, 3HKJ, 3EDX, 3EE0
    Mechanism of the anticoagulant activity of the thrombin mutant W215A/E217A. Gandhi et al (2009) J Biol Chem 284, 24098-24105.
  • 3JZ1, 3JZ2
    The mutant N143P reveals how Na+ activates thrombin. Niu et al (2009) J Biol Chem 284, 36175-36185.
  • 3LU9
    Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1. Gandhi et al (2010) J Biol Chem 285, 15393-15398.
  • 3I77, 3I78
    Combinatorial enzyme design probes allostery and cooperativity in the trypsin fold. Page MJ and Di Cera E (2010) J Mol Biol 399, 306-319.
  • 3MVT
    The role of Zn2+ on the structure and stability of murine adenosine deaminase. Niu et al (2010) J Phys Chem B 114, 16156-16165.
  • 3NXP
    Crystal structure of prethrombin-1. Chen et al (2010) Proc Natl Acad Sci U S A 107, 19278-19283.
  • 3QDZ
    Structural basis of thrombin-PAR interactions. Gandhi et al (2011) IUBMB Life 63, 375-382.
  • 3QGN, 3S7H, 3S7K
    Crystallographic and kinetic evidence of allostery in a trypsin-like protease. Niu et al (2011) Biochemistry 50, 6301-6307.
  • 3R3G
    Rigidification of the autolysis loop enhances Na+ binding to thrombin. Pozzi et al (2011) Biophys Chem 159, 6-13.
  • 3SQE, 3SQH
    Crystal structures of prethrombin-2 reveal alternative conformations under identical solution conditions and the mechanism of zymogen activation. Pozzi et al (2011) Biochemistry 50, 10195-10202.
  • 4DT7
    Exposure of R169 controls protein C activation and autoactivation. Pozzi et al (2012) Blood 120, 664-670.
  • 4H6T, 4HFY, 4H6S, 4HFP
    Autoactivation of thrombin precursors. Pozzi N et al. (2013) J Biol Chem, 288, 11601-11610.
  • 4HZH
    Crystal structure of prothrombin reveals conformational flexibility and mechanism of action. Pozzi N et al. (2013) J Biol Chem, 288, 22734-22744.
  • 4MLF
    Essential role of conformational selection in ligand binding. Vogt AD et al. (2014) Biophys Chem. 186, 13-21.
  • 4NZQ, 4O03
    The linker connecting the two kringles plays a key role in prothrombin activation. Pozzi N et al. (2014) Proc Natl Acad Sci USA. 111, 7630-7635.
  • 4RKJ, 4RKO
    Why ser and not thr brokers catalysis in the trypsin fold. Pelc L et al. (2015) Biochemistry. 54, 1457-1464.