By the same authors

From the same journal

Structural insight into the mechanism of streptozotocin inhibition of O-GlcNAcase

Research output: Contribution to journalArticlepeer-review

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Publication details

DatePublished - 31 Mar 2009
Issue number5
Number of pages5
Pages (from-to)627-631
Original languageEnglish


Despite decades of its use in diabetes research, the mechanism of cytotoxicity of streptozotocin (STZ) toward pancreatic P-islet cells has remained a topic of discussion. Although STZ toxicity is likely a function of its capacity to promote DNA alkylation, it has been proposed that STZ induces pancreatic p-cell death through O-GlcNAcase inhibition. In this report, we explore the binding mode of STZ to a close homolog of human O-GlcNAcase, BtGH84 from Bacteroides thetaiotaomicron. Our results show that STZ binds in the enzyme active site in its intact form, without the formation of a covalent adduct, consistent with solution studies on BtGH84 and human O-GlcNAcase, as well as with structural work on a homolog from Clostridium perfringens. The active site of the BtGH84 is considerably deformed upon STZ binding and as a result the catalytic machinery is expelled from the binding cavity. (C) 2008 Elsevier Ltd. All rights reserved.

    Research areas

  • Streptozotocin, O-GlcNAc, Diabetes, Inhibitor, 3-D structure, Carbohydrate-active enzyme, BETA-CELL DEATH, N-ACETYLGLUCOSAMINE, DIABETOGENIC ACTION, PROTEINS, GLUCOSAMINIDASE, BLOCKS, ANALOG, MIN6, DNA

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