Lee, Jin Kak Han, Won Seok Lee, Jun-Seok Kim, Yong-Sam Ko, Jeong-Heon Yoo, Jong Shin Yoon, Chang No 2024-01-20T02:02:14Z 2024-01-20T02:02:14Z 2021-09-01 2017-03 0253-2964 https://pubs.kist.re.kr/handle/201004/122988 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 beta 1,6-Nacetylglucosamine (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 beta 1,6GlcNAc linkage to the core glycan on the interaction of TIMP-1 with MMP2. The gelatinase inhibitory activity is decreased when additional a beta 1,6-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. English 대한화학회 beta 1,6-GlcNAc Linkage to the Core Glycan on TIMP-1 Affects Its Gelatinase Inhibitory Activities: Aberrantly Glycosylated TIMP-1MMP2 Complex Modeling Shows Weaker Interaction Compared to Bi-antennary Glycosylated TIMP-1 Article 10.1002/bkcs.11096 1 Bulletin of the Korean Chemical Society, v.38, no.3, pp.384 - 388 Bulletin of the Korean Chemical Society 38 3 384 388 N scie scopus kci ART002205984 000397172400014 2-s2.0-85028276492 Chemistry, Multidisciplinary Chemistry Article MATRIX-METALLOPROTEINASE-9 PROGRESSION MECHANISM INVASION TISSUE INHIBITOR MATRIX METALLOPROTEINASE-2 CANCER METASTASIS EXPRESSION MICE Metalloproteinase-1 Glycan structure Glycan interaction beta 1,6-N-acetylglucosamine linkage