Appeal No. 1998-0053
Application 08/444,628
Goldberg discloses the full length 92 kDa gelatinase. The 92 kDa gelatinase is
structurally related to the 72 kDa gelatinase, but is unique among matrix
metalloproteinases in having a 54 amino acid proline-rich domain homologous to the "-2
chain of type V collagen. Figure 6 shows the structural domains shared by the 92 kDa and
72 kDa gelatinases in alignment; the two enzymes share some sequence similarity but the
92 kDa gelatinase contains three potential N-glycosylation sites not found in the 72 kDa
gelatinase and is fully glycosylated.
O’Connell assesses the role of the carboxyl-terminal collagen- and hemopexin-like
domains of the 92 kDa gelatinase. Deletion of these domains, which correspond to
carboxy-terminal amino acids 444-707, does not affect the catalytic activity of the enzyme,
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but does affect the rate of activation in the presence of the inhibitor TIMP-1. O’Connell
also discloses activation of the carboxy-terminal truncated protein to delete various
portions of the amino-terminal, including a deletion corresponding to amino acids 1-105.
Murphy assesses the role of the fibronectin-like domain of the 72 kDa gelatinase.
A deletion mutant lacking the fibronectin-like domain was unable to bind collagen or
gelatin; once activated, the deletion mutant exhibited markedly impaired ability to degrade
gelatin. Page 6634, left-hand column, and page 6635, left-hand column.
Liotta teaches that a region of the amino terminus of the 72 kDa gelatinase acts as
an intrinsic enzyme inhibitor when the enzyme is in a latent state.
5Tissue Inhibitor of Metalloproteinase-1.
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