Model structure for the inflammatory protein C5a.

The complement cleavage product C5a is a potent stimulant of inflammatory processes; thus, inhibition of C5a activity is of therapeutic interest. The three-dimensional structure of the major portion of C5a was modeled from the homologous C3a crystal structure by comparative modeling techniques. The model shows that core residues of C5a are completely conserved, while external residues differ from C3a. Even though the amino-terminal 12 residues of C3a are disordered in the crystal, this sequence in C5a may form an amphipathic helix. The distribution of species sequence differences in the complete C5a structure suggests a possible receptor binding site.

[1]  L. Sieker,et al.  Restrained least-squares refinement of Themiste dyscritum methydroxohemerythrin at 2.0 Å resolution , 1982 .

[2]  R. Huber,et al.  Crystal structure analysis and molecular model of human C3a anaphylatoxin. , 1980, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[3]  R. Henderson,et al.  Three-dimensional model of purple membrane obtained by electron microscopy , 1975, Nature.

[4]  B. W. Erickson,et al.  Human C5a-related synthetic peptides as neutrophil chemotactic factors. , 1979, Biochemical and biophysical research communications.

[5]  D. Shotton,et al.  Three-dimensional Structure of Tosyl-elastase , 1970, Nature.

[6]  D. Osguthorpe,et al.  Structure, energetics and dynamics of ligand binding to dihydrofolate reductase. , 1982, Biochemical Society Transactions.

[7]  T. Hugli,et al.  Human C5a and C5a analogs as probes of the neutrophil C5a receptor. , 1980, Molecular immunology.

[8]  Arnold T. Hagler,et al.  Computer simulation of the conformational properties of oligopeptides. Comparison of theoretical methods and analysis of experimental results , 1979 .

[9]  D. Phillips,et al.  A possible three-dimensional structure of bovine alpha-lactalbumin based on that of hen's egg-white lysozyme. , 1969, Journal of molecular biology.

[10]  A. Lesk,et al.  How different amino acid sequences determine similar protein structures: the structure and evolutionary dynamics of the globins. , 1980, Journal of molecular biology.

[11]  J. Rubin,et al.  Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a). , 1978, Biochemistry.

[12]  B. L. Sibanda,et al.  Computer graphics modelling of human renin , 1984, FEBS letters.

[13]  T. Hugli,et al.  Partial characterization of human C5a anaphylatoxin. I. Chemical description of the carbohydrate and polypeptide prtions of human C5a. , 1976, Journal of immunology.

[14]  B. L. Sibanda,et al.  Three-dimensional structure, specificity and catalytic mechanism of renin , 1983, Nature.

[15]  C. Gerard,et al.  Amino acid sequence of the anaphylatoxin from the fifth component of porcine complement. , 1980, The Journal of biological chemistry.

[16]  T. Hugli,et al.  Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. , 1978, The Journal of biological chemistry.

[17]  H. Domdey,et al.  Characterization of the mRNA and cloned cDNA specifying the third component of mouse complement. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Greer Comparative model-building of the mammalian serine proteases. , 1981, Journal of molecular biology.

[19]  C. Gerard,et al.  Response of human neutrophils to C5a: a role for the oligosaccharide moiety of human C5ades Arg-74 but not of C5a in biologic activity. , 1981, Journal of immunology.

[20]  J. Greer,et al.  Model for haptoglobin heavy chain based upon structural homology. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J Greer,et al.  Model of a specific interaction. Salt-bridges form between prothrombin and its activating enzyme blood clotting factor Xa. , 1981, Journal of molecular biology.

[22]  T. Hugli,et al.  The primary structure of porcine C3a anaphylatoxin. , 1976, Journal of immunology.

[23]  P. Y. Chou,et al.  Empirical predictions of protein conformation. , 1978, Annual review of biochemistry.