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Titolo:
TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2(ADAM-TS5)
Autore:
Kashiwagi, M; Tortorella, M; Nagase, H; Brew, K;
Indirizzi:
Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA Univ Miami Miami FL USA 33101 ept Biochem & Mol Biol, Miami, FL 33101 USA Univ London Imperial Coll Sci Technol & Med, Sch Med, Kennedy Inst Rheumatol, London W6 8LH, England Univ London Imperial Coll Sci Technol & Med London England W6 8LH ngland
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 16, volume: 276, anno: 2001,
pagine: 12501 - 12504
SICI:
0021-9258(20010420)276:16<12501:TIAPIO>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
METALLOPROTEINASES-3 GENE-EXPRESSION; HUMAN TISSUE INHIBITOR; AMINO-TERMINAL DOMAIN; HUMAN SYNOVIAL-FLUID; MATRIX METALLOPROTEINASE; IN-VITRO; ARTICULAR CHONDROCYTES; ESCHERICHIA-COLI; ADAMTS FAMILY; CARTILAGE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Brew, K Florida Atlantic Univ, Dept Biomed Sci, 777 Glades Rd, Boca Raton,FL 33431 USA Florida Atlantic Univ 777 Glades Rd Boca Raton FL USA 33431 31 USA
Citazione:
M. Kashiwagi et al., "TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2(ADAM-TS5)", J BIOL CHEM, 276(16), 2001, pp. 12501-12504

Abstract

The proteoglycan aggrecan is an important major component of cartilage matrix that gives articular cartilage the ability to withstand compression, Increased breakdown of aggrecan is associated with the development of arthritis and is considered to be catalyzed by aggrecanases, members of the ADAM-TS family of metalloproteinases. Four endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate the activities of functional matrix metalloproteinases (MMPs), enzymes that degrade most components of connective tissue, but no endogenous factors responsible for the regulation of aggrecanases have been found. We show here that the N-terminal inhibitory domain of TIMP-3, a member of the TIMP family that has functional properties distinct from other TIMPs, is a strong inhibitor of human aggrecanases 1 and 2, with K-i values in the subnanomolar range. This truncated inhibitor, which lacks the C-terminal domain that is responsible for interactions with molecules other than active metalloproteinases, is produced at high yield by bacterial expression and folding from inclusion bodies. This provides a starting point for developing a biologically available aggrecanase inhibitor suitable for the treatment of arthritis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 13:45:50