Studies on the active site of human leukocytic pyrogen.
Leukocytic pyrogen, a polypeptide produced by phagocytic mononuclear cells, is thought to be the endogenous mediator of fever. In addition to its effects on thermoregulation, leukocytic pyrogen has been shown to induce synthesis of acute-phase proteins, increase lymphocyte blastogenesis to mitogens, and cause release of neutrophil-specific granule contents. Despite its important role in biologic responses, little is known concerning the structure-function relationship of the molecule. In the present studies several protein-modifying conditions were used in order to examine specific amino acid participation at the active site. Because the state of purity of leukocytic pyrogen may be critical during certain reaction conditions, highly purified preparations were used. Experiments suggest that the active site requires the gamma-carboxyl group of glutamic acid and that blocking arginine reduces both the pyrogenic and neutrophil releasing properties of the molecule. Other studies demonstrate that the pyrogenicity of human leukocytic pyrogen is not due to serine esterase or carboxypeptidase B activity and that the 15,000-dalton molecule may be a glycoprotein. These experiments provide further evidence that the lymphocyte-activating and neutrophil-granule-releasing properties of human leukocytic pyrogen require the same active site which produces fever.
D001120:Arginine / Q000378:metabolism; D001665:Binding Sites; D001711:Biotransformation / Q000187:drug effects; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000378:metabolism; D006219:Halogens / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D007375:Interleukin-1; D007555:Isoxazoles / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011506:Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D006219:Halogens; D007202:Indicators and Reagents; D007375:Interleukin-1; D007555:Isoxazoles; D011506:Proteins; C008270:leukocyte endogenous mediator; C009686:N-ethyl-5-phenylisoxazolium-3'-sulfonate; D014443:Tyrosine; D010664:Phenylmethylsulfonyl Fluoride; D001120:Arginine; D002268:Carboxypeptidases; D043424:Carboxypeptidase B