Protease Inhibitors and Prohormone Processing
Authors: Ann Danoff
Journal: Annals of Internal Medicine (2000)

Letters19 September 2000Protease Inhibitors and Prohormone ProcessingAnn Danoff, MD and Wai Lam W. Ling, PhDAnn Danoff, MDBronx-Lebanon Hospital Center; Bronx, NY 10457 (Danoff)Schering-Plough Research Institute; Union, NJ 07083 (Ling)Search for more papers by this author and Wai Lam W. Ling, PhDBronx-Lebanon Hospital Center; Bronx, NY 10457 (Danoff)Schering-Plough Research Institute; Union, NJ 07083 (Ling)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-6-200009190-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Stricker and Goldberg's comments on the distinctive substrate specificities of aspartic and serine proteases. We agree it is unlikely that inhibitors of an aspartyl protease, such as the HIV protease inhibitors, would interfere with proteolytic events usually performed by serine proteases, such as the prohormone-converting enzymes. However, several examples of nonstringent prohormone processing events have been reported. In particular, evidence suggests that the yeast aspartyl protease, Yap3, is capable of accurate endoproteolysis of both prosomatostatin (1) and proopiomelanocortin (2), functions usually performed by the prohormone convertases. In addition, as noted in a previous correspondence between Stricker ...References1. Bourbonnais Y, Germain D, Ash J, Thomas DY. Cleavage of prosomatostatins by the yeast Yap3 and Kex 2 endoprotease. Biochimie. 1994;76:226-33. CrossrefMedlineGoogle Scholar2. Cool DR, Louie DY, Loh YP. Yeast aspartic protease 3 is sorted to secretory granules and activated to process proopiomelanocortin in PC 12 cells. Endocrinology. 1996;137:5441-6. CrossrefMedlineGoogle Scholar3. Stricker RB, Goldberg B. Fat accumulation and HIV-1 protease inhibitors. Lancet. 1998;352:1392. CrossrefMedlineGoogle Scholar4. Poorman RA, Tomasselli AG, Heinrikson RL, Kezdy FJ. A cumulative specificity model for proteases from human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base. J Biol Chem. 1991;266:14554-61. CrossrefMedlineGoogle Scholar5. Yarasheski KE, Tebas P, Sigmund C, Dagogo-Jack S, Bohrer A, Turk J, et al . Insulin resistance in HIV protease inhibitor-associated diabetes. J Acquir Immune Defic Syndr. 1999;21:209-16. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Bronx-Lebanon Hospital Center; Bronx, NY 10457 (Danoff)Schering-Plough Research Institute; Union, NJ 07083 (Ling) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoProtease Inhibitors Do Not Interfere with Prohormone Processing Ann Danoff and Wai Lam W. Ling Protease Inhibitors and Prohormone Processing Raphael B. Stricker and Billi Goldberg Metrics 19 September 2000Volume 133, Issue 6Page: 483KeywordsHIVInsulin resistanceNucleosidesProhormonesProtease inhibitor therapyProtease inhibitorsProteasesSerine proteasesSpecificityToxicity ePublished: 19 September 2000 Issue Published: 19 September 2000 CopyrightCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...