UBC Logo. Click to go to the University of British Columbia Home Page.
  Click here to access the Overall Lab Intranet
Tantalus Range, Bowen Island, Howe Sound and Sunshine Coast, BC, Canada. Click to bring up a really nice picture of the Tantalus Range.
UBC, located amidst Pacific Spirit Park on the tip of Point Grey, Vancouver. Click to view a picture of sunset over the Overall Lab.

Click here to go to the Overall Lab Home Page and to see the Overall Lab in all the seasons Click here to go see seminar titles and pictures of speakers visiting or who have visited the Overall Lab Click here to obtain contact information for Chris Overall and to see pictures and access links to sights in Vancouver Click here to read about the Research Interests of Chris Overall and the Overall Lab and to access the Overall Lab publications pdf library

Click here to enter the TIMP Home Page of the Overall lab web site Click here to enter the MMP Home Page of the Overall Lab web site Click here to go to the Links Page of the Overall Lab web site Click here to view QuickTime movies of social events, Lab Ski Day, our volley ball team and happy workers in the Overall Lab Click here to see pictures of the Laboratory of Chris Overall and the happy workers Click here to see pictures of the Overall Lab personnel and to enter their individual web pages with project details, papers and lots of pictures Click here to see the latest papers In Press from the Overall Lab and to download pdfs Click here to view a list of meetings and conferences related to MMPs, proteases and proteomics Click here to go to the Overall Lab MMP Gordon Research Conference Home Page with program details, speakers and lots of pictures
Click here to enter the 2003 MMP Gordon Research Conference Home Page of the Overall Lab web site with programs, speakers and lots of pictures

 

 

Click here to Email the Webmaster with comments, suggestions, or brocken links
webmaster
Selected Publications from the Overall Lab and PDF Library
 

Gayle R. Pelman, Charlotte, J. Morrison, Christopher M. Overall
Pivotal Molecular Determinants of Peptidic and Collagen Triple Helicase Activities Reside in the S3’ Subsite of Matrix Metalloproteinase 8 (MMP 8):
THE ROLE OF HYDROGEN BONDING POTENTIAL OF ASN188 AND TYR189 AND THE CONNECTING CIS BOND
J. Biol. Chem. 280, 2370-2377 [PDF]

 
Christopher M. Overall
Dilating the Degradome: Matrix Metalloproteinase-2 Cuts to the Heart of the Matter
Biochemical Journal 383 (3), e5-e7. Invited commentary
[PDF]
 Mounted on the Internet with the permission of The Biochemical Society 2004

Eric M. Tam, Todd R. Moore, Georgina S. Butler,
and Christopher M. Overall
Characterization of the Distinct Collagen Binding and Cleavage Mechanisms of Matrix Metalloproteinase 2 and 14 (gelatinase A and MT1-MMP): The Differential roles of the MMP Hemopexin C Domains and the MMP-2 Fibronectin Type II modules in Collagen Triple Helicase Activities
J. Biol. Chem., 279, 43336-43344 [Reprint/PDF]

 
Matthew W. C. Chan, Tarek Y. El Sayegh, Pamela D. Arora, Carol A. Laschinger, Christopher M. Overall, Charlotte Morrison, and Christopher A. McCulloch
Regulation of Intercellular Adhesion Strength in Fibroblasts
J. Biol. Chem., Jul 2004; 10.1074/jbc.M406631200 [Reprint/PDF]

Christopher M. Overall, Eric M. Tam, Reinhild Kappelhoff, Andrea Connor, Tom Ewart, Charlotte J. Morrison, Xose Puente, Carlos López-Otín, and Arun Seth
Protease Degradomics: Mass Spectrometry Discovery of Protease Substrates and the CLIP-CHIP, a Dedicated DNA Microarray of all Human Proteases and Inhibitors
Biological Chermistry 385 (6), 493-504 (2004).
[Preprint/PDF]
CLIP-CHIP. The first dedicated and complete human protease and inhibitor DNA microarray.
Eric M. Tam, Charlotte J. Morrison, Yi I. Wu, M. Sharon Stack, and Christopher M. Overall
Membrane Protease Proteomics: Isotope-coded Affinity Tag MS Identification of Undescribed MT1-Matrix Metalloproteinase Substrates
Proc. Natl. Acad. Sci. USA 101 (18), 6917-6922 (2004).
[Preprint/PDF] 		Protease substrate discovery: Flow diagram of MS/MS analysis of ICAT labelled proteins in cells transfected with MT1-MMP

Georgina S. Butler, Eric M. Tam and Christopher M. Overall
The Canonical Methionine 392 Of Matrix Metalloproteinase 2 (Gelatinase A) Is Not Required For Catalytic Efficiency Or Structural Integrity: Probing the Role of the Methionine-turn in the Metzincin Metalloprotease Superfamily
Journal of Biological Chemistry 279, 15,615-15,620.
[Preprint/PDF] 		 
Milagros Balbín, Antonio Fueyo, Angus M. Tester, Alberto M. Pendás, Ana S. Pitiot, Aurora Astudillo, Christopher M. Overall, Steve Shapiro, & Carlos López-Otín 2003
Loss of Collagenase-2 Confers Increased Skin Tumour Susceptibility to Male Mice
Nature Genetics 35, 252-257 (2003).
[Reprint/PDF]
Cover of Nature Genetics November 2003
Kunyan Zhang, G. Angus McQuibban, Claudia Silva, Georgina S. Butler, James B. Johnston, Janet Holden, Ian Clark-Lewis, Christopher M. Overall* and Christopher Power* 2003
HIV-induced Metalloproteinase Cleavage of the Chemokine SDF-1a Causes Neurodegeneration
*Joint Communicating Authors
Nature Neuroscience 6, 1064-1071 (2003).
[Reprint/PDF] [HTML]
MMP-2 induces neurodegeneration by a novel apoptotic pathway initiated by ectopic MMP-2 activity in the brain upon HIV infection and executed by cleaved SDF that progresses to HIV dementia
Xose S. Puente, Luis, M. Sanchez, Christopher M. Overall and Carlos López-Otín 2003.
Human and Mouse Proteases: A Comparative Genomic Approach
Nature Reviews Genetics 4, 544-558.
[Reprint (PDF)]
[Reprint HTML]
Summary [HTML]
Degradomic Tables [HTML]

The Protease Wheel showing all members of the human and mouse degradomes
Veli-Juka Uitto, Christopher M. Overall, and Chris McCulloch 2003.
Proteolytic Host Cell Enzymes in Gingival Crevicular Fluid
Periodontology 2000 31: 77-104. [Reprint (PDF)]
  		 
Heidi S.-T. Kai, Georgina S. Butler, Charlotte J. Morrison, Angela E. King, Gayle R. Pelman, and Christopher M. Overall 2002.
Utilization of a Novel Recombinant Myoglobin Fusion Protein Expression System to Characterize the Tissue Inhibitor of Metalloproteinase (TIMP)-4 and TIMP-2 C-terminal Domain and Tails by Mutagenesis.
THE IMPORTANCE OF ACIDIC RESIDUES IN BINDING THE MMP-2 HEMOPEXIN C DOMAIN
J. Biol. Chem. 277: 48696-48707. [Reprint (PDF)]
Recombinant C-TIMPs can be visually tracked during purification due to the red coloring of the horse heart myoglobin fusion protein.
  

Anna Radomski, Paul Jurasz, Esmond J. Sanders, Heather F. Bigg, Christopher M. Overall,
Dylan R. Edwards and Marek W. Radomski 2002.
Identification, Regulation and Role of Tissue Inhibitor of Metalloproteinases-4 (TIMP-4) in Human Platelets
British Journal of Pharmacology. 137: 1330-1338 [Reprint (PDF)]

  

Eric M. Tam, Yi I. Wu, Georgina S. Butler, M. Sharon Stack, and Christopher M. Overall 2002.
Collagen Binding Properties of the MT1-MMP Hemopexin C domain:
The Ectodomain of the 44-kDa Autocatalytic Fragment of MT1-MMP Inhibits Cell Invasion by Disrupting Native Type I Collagen Cleavage
J. Biol. Chem. 277: 39005-39014. [Reprint (PDF)]
MT1-MMP hemopexin C domain constructs and linker peptide analogs. A, the domain structures of pro-MT1-MMP (i) and 44-kDa MT1-MMP (ii) are shown in a linear diagram.

  



Christopher M. Overall and Carlos López-Otín 2002.
Strategies for MMP Inhibition in Cancer:
Innovations for the Post-Trial Era
Nature Reviews Cancer 2: 657-672.
 [Reprint (PDF)][Article Online (HTML)]
[Commentary (PDF), Online (HTML)]
 [Nature Reviews Cancer September 2002 Issue]
 
G. Angus McQuibban, Julie P. Wong, Jiang-Hong Gong, John L. Wallace, Ian Clark-Lewis, and Christopher M. Overall 2002.
Matrix Metalloproteinase Processing of Monocyte Chemoattractant
Proteins Generates CC Chemokine Receptor Antagonists with
Anti-inflammatory Properties in vivo
 Blood 100: 1160-1167. [Reprint (PDF)]

Cutting the head off chemokines - Blood 100: 1110.
[Commentary (PDF)]

  

Carlos López-Otín and Christopher M. Overall 2002.
Protease Degradomics: A New Challenge for Proteomics
Nature Reviews Molecular Cell Biology. 3: 509-519. [Reprint (PDF)][Online (HTML)][Nature Reviews Molecular Cell Biology July 2002 Issue]
 
Christopher M. Overall 2002.
Molecular Determinants of Metalloproteinase Substrate Specificity: Matrix Metalloproteinase Substrate Binding Domains, Modules and Exosites
Molecular Biotechnology. 22: 51-86. (Invited Review).
[Reprint (PDF)]

 

Christopher M. Overall, G. Angus McQuibban, and Ian Clark-Lewis 2002.
Discovery of Chemokine Substrates for Matrix Metalloproteinases by Exosite Scanning: A New Tool for Degradomics
Biological Chemistry. 383:1059-1066. [Reprint (PDF)]

  
Georgina S. Butler, Derek Sim, Eric Tam, Dana Devine, and Christopher M. Overall 2002.
Mannose Binding Lectin (MBL) Mutants are Susceptible to Matrix Metalloproteinase Proteolysis: Potential Role in Human MBL Deficiency
J. Biol. Chem. 277: 17511-17519. [Reprint (PDF)]
 

Shin Numao, Robert Maurus, Gary Sidhu, Yili Wang, Christopher M. Overall, Gary D. Brayer, and Stephen G. Withers
Probing the Role of the Chloride Ion in the Mechanism of Human Pancreatic alpha-Amylase
Biochemistry 2002 41: 215-225. [Reprint (PDF)]
 
S. Saad, D.J. Gottlieb, K.F. Bradstock, C.M. Overall, and L.J. Bendall 2002.
Cancer Cell-associated Fibronectin Induces Release of Matrix Metalloproteinase-2 from Normal Fibroblasts.
Cancer Res 62: 283-289. [Reprint (PDF)]		  
Charlotte J. Morrison, Georgina S. Butler, Heather F. Bigg, Clive R. Roberts, Paul D. Soloway, and Christopher M. Overall 2001.
Cellular Activation of MMP-2 (Gelatinase A) by MT2-MMP Occurs via a TIMP-2-independent Pathway J. Biol. Chem. 276: 47402-47410. [Reprint (PDF)]
 
G. Angus McQuibban, Georgina S. Butler, Jiang-Hong Gong, Linda Bendall, Christopher Power, Ian Clark-Lewis, and Christopher M. Overall 2001.
Matrix Metalloproteinase Activity Inactivates the CXC Chemokine Stromal Cell-derived Factor-1
J. Biol. Chem. 276: 43503-43508. [Reprint (PDF)]
 
Bigg, H.F., Morrison, C.J., Butler, G.S., Bogoyevitch, M.A., Wang, Z., Soloway, P.D., and Overall, C.M. 2001.
Tissue Inhibitor of Metalloproteinase-4 Inhibits But Does Not Support the Activation of Gelatinase A Via Efficient Inhibition of Membrane Type 1-Matrix Metalloproteinase
Cancer Res. 61: 3610-3618. [Reprint (PDF)]

    
Shawn M. Ellerbroek, Yi I. Wu, Christopher M. Overall, and M. Sharon Stack 2001.
Functional Interplay between Type I Collagen and Cell Surface Matrix Metalloproteinase
Activity
J. Biol. Chem. 276: 24833-24842. [Reprint (PDF)]

  
Tiebang Kang, Jun Yi, Athena Guo, Xing Wang, Christopher M. Overall, Weiping Jiang, Robert Elde, Niels Borregaard, and Duanqing Pei 2001.
Subcellular Distribution and Cytokine- and Chemokine-regulated Secretion of Leukolysin/MT6-MMP/MMP-25 in Neutrophils
J. Biol. Chem. 276: 21960-21968. [Reprint (PDF)]

  
G. Angus McQuibban, Jiang-Hong Gong, Eric M. Tam, Christopher A. G. McCulloch, Ian Clark-Lewis, and Christopher M. Overall 2000.
Inflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3
Science 289: 1202-1206. [Reprint (PDF)]

    
Marta Toth, M. Margarida Bernardo, David C. Gervasi, Paul D. Soloway, Zhiping Wang, Heather F. Bigg, Christopher M. Overall, Yves A. DeClerck, Harald Tschesche, Michael L. Cher, Stephen Brown, Shahriar Mobashery, and Rafael Fridman 2000.
Tissue Inhibitor of Metalloproteinase (TIMP)-2 Acts Synergistically with Synthetic Matrix Metalloproteinase (MMP) Inhibitors but Not with TIMP-4 to Enhance the (Membrane Type 1)-MMP-dependent Activation of Pro-MMP-2 J. Biol. Chem. 275: 41415-41423. [Reprint (PDF)]

    
Christopher M. Overall, Eric Tam, G. Angus McQuibban, Charlotte Morrison, U. Margaretha Wallon, Heather F. Bigg, Angela E. King, and Clive R. Roberts 2000.
Domain Interactions in the Gelatinase A·TIMP-2·MT1-MMP Activation Complex. THE ECTODOMAIN OF THE 44-kDa FORM OF MEMBRANE TYPE-1 MATRIX METALLOPROTEINASE DOES NOT MODULATE GELATINASE A ACTIVATION
J. Biol. Chem. 275: 39497-39506. [Reprint (PDF)]


    
Stereo drawing showing the overall polypeptide chain fold of human pancreatic -amylase. The central feature of this structure is an eight-stranded parallel -barrel that forms the bulk of domain A and contains the active site region.  
G.D. Brayer, G. Sidhu, R. Maurus, E.H. Rydberg, C. Braun, Y. Wang, N.T. Nguyen, C.M. Overall, and S.G. Withers 2000.
Subsite Mapping of the Human Pancreatic alpha-Amylase Active Site Through Structural, Kinetic, and Mutagenesis Techniques
Biochemistry. 39: 4778-91. [Reprint (PDF)]

  
Christopher M. Overall, Angela E. King, Douglas K. Sam, Aldrich D. Ong, Tim T. Y. Lau, U. Margaretha Wallon, Yves A. DeClerck, and Juliet Atherstone 1999.
Identification of the Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) Binding Site on the Hemopexin Carboxyl Domain of Human Gelatinase A by Site-directed Mutagenesis. THE HIERARCHICAL ROLE IN BINDING TIMP-2 OF THE UNIQUE CATIONIC CLUSTERS OF HEMOPEXIN MODULES III AND IV
J. Biol. Chem. 274: 4421-4429. [Reprint (PDF)]
 
E.H. Rydberg, G. Sidhu, H.C. Vo, J. Hewitt, H.C.F. Côté, Y. Wang, S. Numao, R.T.A. MacGillivray, C.M. Overall, G.D. Brayer, and S.G. Withers 1999.
Cloning, Mutagenesis and Structural Analysis of Human Pancreatic alpha-Amylase Expressed in Pichia Pastoris.
Protein Science 8: 635-643. [Reprint (PDF)]

  
Bjorn Steffensen, Heather F. Bigg, and Christopher M. Overall 1998.
The Involvement of the Fibronectin Type II-like Modules of Human Gelatinase A in Cell Surface Localization and Activation
J. Biol. Chem. 273: 20622-20628. [Reprint (PDF)]

    
Heather F. Bigg, Y. Eric Shi, Yiliang E. Liu, Bjorn Steffensen, and Christopher M. Overall 1997.
Specific, High Affinity Binding of Tissue Inhibitor of Metalloproteinases-4 (TIMP-4) to the COOH-terminal Hemopexin-like Domain of Human Gelatinase A. TIMP-4 BINDS PROGELATINASE A AND THE COOH-TERMINAL DOMAIN IN A SIMILAR MANNER TO TIMP-2
J. Biol. Chem. 272: 15496-15500. [Reprint (PDF)]

    
U. Margaretha Wallon and Christopher M. Overall 1997.
The Hemopexin-like Domain (C Domain) of Human Gelatinase A (Matrix Metalloproteinase-2) Requires Ca2+ for Fibronectin and Heparin Binding. BINDING PROPERTIES OF RECOMBINANT GELATINASE A C DOMAIN TO EXTRACELLULAR MATRIX AND BASEMENT MEMBRANE COMPONENTS
J. Biol. Chem. 272: 7473-7481. [Reprint (PDF)]

    
Christopher M. Overall 1995.
Repression of tissue inhibitor of matrix metalloproteinase expression by all-trans-retinoic acid in rat bone cell populations: comparisons with transforming growth factor-ß1.
J. Cell. Physiol.164: 17-25.

  
Bjorn Steffensen, U. Margaretha Wallon, and Christopher M. Overall 1995.
Extracellular matrix binding properties of recombinant fibronectin type II-like modules of human 72-kDa gelatinase/type IV collagenase. High affinity binding to native type I collagen but not native type IV collagen
J. Biol. Chem. 270: 11555-11566. [Reprint (PDF)]

  
Christopher M. Overall, Jeffrey L. Wrana, and Jaro Sodek 1991.
Transcriptional and post-transcriptional regulation of 72-kDa gelatinase/type IV collagenase by transforming growth factor-beta 1 in human fibroblasts. Comparisons with collagenase and tissue inhibitor of matrix metalloproteinase gene expression
J. Biol. Chem. 266: 14064-14071. [Reprint (PDF)]

  
Christopher M. Overall and Jaro Sodek 1990.
Concanavalin A produces a matrix-degradative phenotype in human fibroblasts. Induction and endogenous activation of collagenase, 72-kDa gelatinase, and Pump-1 is accompanied by the suppression of the tissue inhibitor of matrix metalloproteinases
J. Biol. Chem. 265: 21141-21151. [Reprint (PDF)]

  
Christopher M. Overall, Jeffrey L. Wrana, and Jaro Sodek 1989.
Independent regulation of collagenase, 72-kDa progelatinase, and metalloendoproteinase inhibitor expression in human fibroblasts by transforming growth factor-beta
J. Biol. Chem. 264: 1860-1869. [Reprint (PDF)]

  
R. Khokha, P. Waterhouse, S. Yagel, P.K. Lala, C.M. Overall, G. Norton, and D.T. Denhardt 1989.
Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells.
Science 243: 947-950.
Top		  
   
 
MMP, TIMP, MATRIX, METALLO, PROTEINASE, PROTEASE, KINETICS, ASSAYS, TISSUE INHIBITOR, PROTEOMICS, DEGRADOMICS, GELATINASE, MT-MMP, HEMOPEXIN C DOMAIN
EXOSITE, SUBSTRATE, MUTAGENESIS, PROTEIN ENGINEERING, CHEMOKINE, MASS SPECTROMETRY, ICAT, MOLECULAR BIOLOGY, CANCER, CLIP, MMP-1... MMP-2... MMP-3... MMP-7...
MMP-8... MMP-9... MMP-10... MMP-11... MMP-12Chris Overall Lab, UBC. Copyright © 2003 Canada MMP-13... MMP-14... MMP-15...MMP-16... MMP-17... MMP-18...
MMP-19... MMP-20... MMP-21... MMP-22... MMP-23... MMP-23a... MMP-23b... MMP-24... MMP-25... MMP-26... MMP-27... MMP-28... C-MMP... X-MMP... TIMP-1... TIMP-2... TIMP-3 TIMP-4