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The Resource Discovery of epitopes governing MMP-12 specificity for fibrillar substrates : BINDSIght, a method for determining specific sites of substrate surface interactions, by Mark Oliver Palmier, (electronic resource)

Discovery of epitopes governing MMP-12 specificity for fibrillar substrates : BINDSIght, a method for determining specific sites of substrate surface interactions, by Mark Oliver Palmier, (electronic resource)

Creator
Contributor
Summary
What determines MMP-12 elastase activity? We have found that the fibrillar substrate specificity of MMP-12 involves surfaces ranging beyond the intensively studied active site cleft and S1' pocket. This was achieved by discovery of a novel global analysis method. The BINDSIght method of discovering sites governing specificity uses a combination of bioinformatic and NMR detected assays. Using this new technology to guide a mutagenesis study, new light has been shed on the substrate specificity of MMP-12 toward elastin and collagen (V). Using a novel kinetic methodology I developed for analyzing time domain progress curves, the mutational lesions were compared to wild type MMP-12 by activity assays. Residues F202, T205 and H206 in the strand V to helix B loop appear to be significant factors in the binding and catalytic rate of fluorescent mimics of collagen V and elastin. Surprisingly, the unprimed site residues F185 and G227 show up as important keys in modifying activity on these fibrillar substrates. In the primed site region we show that T239 and K241 also directly contribute to MMP-12 elastin and collagen V activity. Mutating these residues significantly impairs activity upon elastin and collagen V substrate mimics without compromising activity upon a small broad range MMP substrate. Since the entire family of MMPs differ very little in sequence of the active site, it makes sense that exosites contribute to MMP-12 activity
Language
eng
Work
Publication
Extent
1 online resource (285 pages)
Note
  • Title from PDF of title page (University of Missouri--Columbia, viewed on November 23, 2010)
  • The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file
  • Dissertation advisor: Dr. Steven R. Van Doren
  • Vita
Instance
Label
Discovery of epitopes governing MMP-12 specificity for fibrillar substrates : BINDSIght, a method for determining specific sites of substrate surface interactions
Title
Discovery of epitopes governing MMP-12 specificity for fibrillar substrates
Title remainder
BINDSIght, a method for determining specific sites of substrate surface interactions
Statement of responsibility
by Mark Oliver Palmier
Creator
Contributor
Thesis advisor
Subject
Genre
Language
eng
Summary
What determines MMP-12 elastase activity? We have found that the fibrillar substrate specificity of MMP-12 involves surfaces ranging beyond the intensively studied active site cleft and S1' pocket. This was achieved by discovery of a novel global analysis method. The BINDSIght method of discovering sites governing specificity uses a combination of bioinformatic and NMR detected assays. Using this new technology to guide a mutagenesis study, new light has been shed on the substrate specificity of MMP-12 toward elastin and collagen (V). Using a novel kinetic methodology I developed for analyzing time domain progress curves, the mutational lesions were compared to wild type MMP-12 by activity assays. Residues F202, T205 and H206 in the strand V to helix B loop appear to be significant factors in the binding and catalytic rate of fluorescent mimics of collagen V and elastin. Surprisingly, the unprimed site residues F185 and G227 show up as important keys in modifying activity on these fibrillar substrates. In the primed site region we show that T239 and K241 also directly contribute to MMP-12 elastin and collagen V activity. Mutating these residues significantly impairs activity upon elastin and collagen V substrate mimics without compromising activity upon a small broad range MMP substrate. Since the entire family of MMPs differ very little in sequence of the active site, it makes sense that exosites contribute to MMP-12 activity
Cataloging source
MUU
http://library.link/vocab/creatorDate
1951-
http://library.link/vocab/creatorName
Palmier, Mark O.
Degree
Ph. D.
Dissertation year
2008.
Granting institution
University of Missouri--Columbia
Illustrations
illustrations
Index
no index present
Literary form
non fiction
Nature of contents
  • dictionaries
  • bibliography
  • theses
http://library.link/vocab/relatedWorkOrContributorName
Van Doren, Steven
http://library.link/vocab/subjectName
  • Metalloproteinases
  • Antigenic determinants
  • Mutagenesis
  • Emphysema, Pulmonary
  • Aortic aneurysms
Target audience
specialized
Label
Discovery of epitopes governing MMP-12 specificity for fibrillar substrates : BINDSIght, a method for determining specific sites of substrate surface interactions, by Mark Oliver Palmier, (electronic resource)
Instantiates
Publication
Note
  • Title from PDF of title page (University of Missouri--Columbia, viewed on November 23, 2010)
  • The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file
  • Dissertation advisor: Dr. Steven R. Van Doren
  • Vita
Bibliography note
Includes bibliographical references (pages 217-252)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Control code
689998413
Extent
1 online resource (285 pages)
Form of item
online
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Note
MU: Access is limited to the campuses of the University of Missouri.
Other physical details
illustrations
Specific material designation
remote
System control number
(OCoLC)689998413
Label
Discovery of epitopes governing MMP-12 specificity for fibrillar substrates : BINDSIght, a method for determining specific sites of substrate surface interactions, by Mark Oliver Palmier, (electronic resource)
Publication
Note
  • Title from PDF of title page (University of Missouri--Columbia, viewed on November 23, 2010)
  • The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file
  • Dissertation advisor: Dr. Steven R. Van Doren
  • Vita
Bibliography note
Includes bibliographical references (pages 217-252)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Control code
689998413
Extent
1 online resource (285 pages)
Form of item
online
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Note
MU: Access is limited to the campuses of the University of Missouri.
Other physical details
illustrations
Specific material designation
remote
System control number
(OCoLC)689998413

Subject

Genre

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