4z6a

Crystal Structure of a FVIIa-Trypsin Chimera (YT) in Complex with Soluble Tissue Factor

spinqualitylabelsall models 4z6a, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z6a is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: 0Z6, BGC, CA, CIT, FUC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TF_HUMAN Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade. Publication Abstract from PubMed The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic properties. Extensive studies have revealed two putative pathways for this allosteric communication. Here we provide further details of this allosteric communication by investigating FVIIa loop swap variants containing the 170-loop of trypsin that display TF-independent enhanced activity. Using x-ray crystallography, we show that the introduced 170-loop from trypsin directly interacts with the FVIIa active-site, stabilizing segment 215-217a and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215-217 conformation is pivotal to the enhanced activity of the FVIIa variants. We speculate that the allosteric regulation of FVIIa activity by TF binding follows a similar path in conjunction with N-terminus insertion, suggesting a more complete molecular basis of TF-mediated allosteric enhancement of FVIIa activity. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-Mediated Allosteric Regulation of Factor VIIa Activity.,Sorensen AB, Madsen JJ, Svensson LA, Pedersen AA, Ostergaard H, Overgaard MT, Olsen OH, Gandhi PS J Biol Chem. 2015 Dec 22. pii: jbc.M115.698613. PMID:26694616 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tissue factor

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