PMID- 10551873
OWN - NLM
STAT- MEDLINE
DCOM- 20000103
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 46
DP  - 1999 Nov 12
TI  - Catalytic activities and substrate specificity of the human membrane type 4
      matrix metalloproteinase catalytic domain.
PG  - 33043-9
AB  - Membrane type (MT) matrix metalloproteinases (MMPs) are recently recognized
      members of the family of Zn(2+)- and Ca(2+)-dependent MMPs. To investigate the
      proteolytic capabilities of human MT4-MMP (i.e. MMP-17), we have cloned DNA
      encoding its catalytic domain (CD) from a breast carcinoma cDNA library. Human
      membrane type 4 MMP CD (MT4-MMPCD) protein, expressed as inclusion bodies in
      Escherichia coli, was purified to homogeneity and refolded in the presence of
      Zn(2+) and Ca(2+). While MT4-MMPCD cleaved synthetic MMP substrates
      Ac-PLG-[2-mercapto-4-methylpentanoyl]-LG-OEt and Mca-PLGL-Dpa-AR-NH(2) with
      modest efficiency, it catalyzed with much higher efficiency the hydrolysis of a
      pro-tumor necrosis factor-alpha converting enzyme synthetic substrate,
      Mca-PLAQAV-Dpa-RSSSR-NH(2). Catalytic efficiency with the pro-tumor necrosis
      factor-alpha converting enzyme substrate was maximal at pH 7.4 and was modulated 
      by three ionizable enzyme groups (pK(a3) = 6.2, pK(a2) = 8.3, and pK(a1) = 10.6).
      MT4-MMPCD cleaved gelatin but was inactive toward type I collagen, type IV
      collagen, fibronectin, and laminin. Like all known MT-MMPs, MT4-MMPCD was also
      able to activate 72-kDa progelatinase A to its 68-kDa form. EDTA,
      1,10-phenanthroline, reference hydroxamic acid MMP inhibitors, tissue inhibitor
      of metalloproteinases-1, and tissue inhibitor of metalloproteinases-2 all
      potently blocked MT4-MMPCD enzymatic activity. MT4-MMP is, therefore, a competent
      Zn(2+)-dependent MMP with unique specificity among synthetic substrates and the
      capability to both degrade gelatin and activate progelatinase A.
FAU - Wang, Y
AU  - Wang Y
AD  - Department of Biochemistry, Parke-Davis Pharmaceutical Research Division,
      Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
FAU - Johnson, A R
AU  - Johnson AR
FAU - Ye, Q Z
AU  - Ye QZ
FAU - Dyer, R D
AU  - Dyer RD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chelating Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Enzyme Precursors)
RN  - 0 (Recombinant Proteins)
RN  - 9000-70-8 (Gelatin)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (MMP17 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.- (progelatinase)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Chelating Agents/pharmacology
MH  - Cloning, Molecular
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme Precursors/metabolism
MH  - Escherichia coli
MH  - Gelatin/metabolism
MH  - Gelatinases/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Matrix Metalloproteinases/chemistry/*genetics
MH  - Matrix Metalloproteinases, Membrane-Associated
MH  - Metalloendopeptidases/metabolism
MH  - Molecular Sequence Data
MH  - Protein Folding
MH  - Recombinant Proteins/chemistry/genetics
MH  - Substrate Specificity
MH  - Zinc/chemistry
EDAT- 1999/11/07 00:00
MHDA- 1999/11/07 00:01
CRDT- 1999/11/07 00:00
PHST- 1999/11/07 00:00 [pubmed]
PHST- 1999/11/07 00:01 [medline]
PHST- 1999/11/07 00:00 [entrez]
AID - 10.1074/jbc.274.46.33043 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 12;274(46):33043-9. doi: 10.1074/jbc.274.46.33043.