Abstract
Matrix metalloproteinases (MMPs) are proteolytic enzymes that can regulate the tumor microenvironment. Metalloproteinase-1 (TIMP-1) is a MMP inhibitor that plays a critical role in the invasion and migration of cancer cells. N-acetylglucosaminyltransferase-V (GnT-V) catalyzes the attachment of a β1,6-N-acetylglucosamine (GlcNAc) linkage to the core glycan, and TIMP-1 has identified target proteins for GnT-V. Recent research reveals that aberrantly glycosylated TIMP-1 showed a weaker inhibition on gelatinase, and that this aberrancy of glycosylation was closely related with cancer cell invasion and metastasis. However, the mechanism of action of glycan modification is not known at the molecular level. In this study, the bi-antennary and aberrant glycan structures were determined by mass spectrometry, and a model of the glycosylated TIMP-1-MMP2 complex was constructed to study the effects of glycosylation on the inhibitory activity of TIMP-1. Then this model was used to examine the effects of attaching a β1,6-GlcNAc linkage to the core glycan on the interaction of TIMP-1 with MMP2. The gelatinase inhibitory activity is decreased when additional a β1,6-GlcNAc moiety is linked to the core glycan on TIMP-1. The modeled structure of the glycosylated TIMP-1-MMP2 complex reveals how aberrant N-linked glycan hinders the interaction of these molecules.
Original language | English |
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Pages (from-to) | 384-388 |
Number of pages | 5 |
Journal | Bulletin of the Korean Chemical Society |
Volume | 38 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2017 Mar 1 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by intramural funding from Korea Institute of Science and Technology (2E26110 and 2E26990) and the Converging Research Center Program through the Ministry of Science, Information & Communication Technology and Future Planning.
Publisher Copyright:
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords
- Glycan interaction
- Glycan structure
- Metalloproteinase-1
- β1,6-N-acetylglucosamine linkage
ASJC Scopus subject areas
- General Chemistry