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Structural superposition of the backbone of the serine protease domain of wild type human activated protein C (purple) or of the Ser360Ala variant of activated protein C (green). Representation is according to thrombin’s standard orientation, i.e. with the active site cleft facing the viewer and the 60loop to the north. The sidechains of the catalytic site residues His57, Asp102 and Ser195 are indicated by thin lines. Access to the active site for FPR-APC is severely hampered by positioning of the FPR-unit (in yellow stick representation, with the transparent atomic surface indicated) , whereas this is less the case for the PMS-APC variant (PMS unit represented as red sticks). For clarity the backbones of the superimposed serine protease domains of FPR-APC and PMS-APC are not shown. Nicolaes, G.A.F., Bock, P.E., Segers, K., Wildhagen, K.C.A.A., Dahlback, B., Rosing, J. (2010) J. Biol. Chem. May 18. 48 |
Detail of the encounter trimeric complex for human Annexin A5. Indicated are the positions of proposed residues that are involved in formation of the trimeric complex. These residues were mutated by site-directed mutagenesis. Mutation of the indicated residues resulted in an Annexin A5 variant that binds to phospholipid membranes only in the monomeric form: no 2D crystalization was observed for this mutant. Ungethum L., Kenis H., Nicolaes G.A.F., Autin L., Stoilova-McPhie S., Reutelingsperger C.P.. (2011) J Biol Chem. 286(3):1903-1910 |
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Docked pose of human activated protein C onto coagulation factor Va at the predominant APC cleavage site around Arg506. From : Nicolaes et al., (2004) Eur J Biochem, 271 (13):2724-36.
Structural Analysis of α1 antitrypsin, illustrating a surface exposed cystein amino acid residue in magenta coloring that is likely subject to post ribosomal modification (Kolarich, D et al . (2006) Transfusion 46(11):1959-77
Just fooling around.....a sandwich dimer of trimers for human Annexin V. Even though this type of organisation was seen for other types of annexins, for annexin V this has not (yet?) been the case.
Detail of the docked pose of thrombin aptamer 1 contacting the exosite I of human thrombin, as is further detailed in: Segers, K., et al.
(2007) J Biol Chem. 282(47):33915-33924
Structural analysis of the SHBG domain of human protein S, and the explanation of the clinical phenotypes of protein S type I and II deficient patients (ten Kate, M.et al. (2008) Human Mutation, 29(7),939-47.
Plastic model impression of the trimeric complex of human Annexin V. Notice the close resemblance of Annexins and peanut cookies!
Structural bioinformatics analysis of the C2 domain of human coagulation factor V. Mutation of the salt-bridged Asp2194 into Gly (As in the factor V R2 haplotype) may influence the formation of a nearby disulphide bridge (Miteva, M.A. et al. (2004) Biophys. J., 86(1): 488- 98
Left: Ribbon plot of the C2 domain open form highlighting the membrane binding loops and displaying the amino acid side chains of the key membrane-binding players. Right: Proposed docked pose for compound 001C07. The small molecule after Surflex and LigandFit consensus docking occupies the phospholipids binding groove thereby impeding membrane interaction. Hydrophobic/aromatic interactions occur with W2063, W2064 and L2116 region. Hydrogen bonds between the side chain of K2060, N2089 and Gln 2182 and the compound carboxylate group are predicted while the fluorobenzene group shows a favorable interaction with either the side chains of either W2064 or R2080. From: Segers, K. et al. (2007) Proc. Natl. Acad. Sci. 104 (31):12697-702
Detail of the active site of Russels Viper Venom, a specific activator of coagulation factor V that is present in the venom of Russel's Viper. The
structure of this enzyme was modelled in our laboratory. On basis of the structure we were able to explain the inhibiton or lack of inhibition
by certain serine protease inhibitors and further we identified certain exosites on the surface of this protein that provide an explanation to
its narrow substrate specificity. Segers, K., Rosing, J., Nicolaes, G.A.F. (2006). Proteins 64(4):968-84
