Author Type

Graduate Student

Date of Award

2008

Document Type

Thesis

Publication Status

Version of Record

Submission Date

October 2026

Abstract

Tissue inhibitors of metalloproteinases (TIMPs) comprise a family of four proteins in humans that modulate the turnover of the extracellular matrix by regulating the activities of endopeptidases that catalyze its degradation, especially the matrix metalloproteinases (MMP). In general, the four TIMPs are broad-spectrum tight binding inhibitors of MMPs with individual differences in specificity. In this study, we attempted to understand the basis of such variation by using membrane type-1 MMP (MT1-MMP) as a model, since it is inefficiently inhibited by TIMP-1 in contrast with the other TIMPs. We designed and engineered mutations in the N-domain of TIMP-1, based on current knowledge of TIMP interactions. By measuring inhibition levels of each mutant against several MMPs, including MT1-MMP, we were able to obtain a triple mutant with an vii improved affinity for MT1-MMP.

Extent

xiii, 135 p. : ill. (some col.).

Comments

by Asmaa Bilal Hamze.|Vita.|Thesis (Ph.D.)--Florida Atlantic University, 2008.|Includes bibliography.|Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.|by Asmaa Bilal Hamze.

Identifier

FADT186296

Format

pdf

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