Rat cathespin dipeptidyl peptidase i (dppi): crystal structure and its uses

A crystallised molecule or molecular complex comprising a rat DPPI protein with the amino acid sequence as shown in SEQ ID NO:

• 1.

A crystallised molecule or molecular complex comprising a protein with at least 37% amino acid sequence identity to the amino acid sequence of rat DPPI protein as shown in SEQ ID NO:

• 1.

The crystal structure of a protein with at least 37% amino acid sequence identity to the amino acid sequence of rat DPPI protein as shown in SEQ ID NO:

• 1.

The crystal structure of a protein with at least 75% amino acid sequence identity to the amino acid sequence of rat DPPI protein as shown in SEQ ID NO:

• 1.

The crystal structure of a protein with an amino acid sequence as shown in SEQ ID NO:

• 1.

The crystal structure of a protein for which the structural co-ordinates of the back bone nitrogen, alpha-carbon and carbonyl carbon atoms of said protein have a root-mean-square deviation from the structural co-ordinates of the equivalent back bone atoms of rat DPPI (as defined in Table 2) of less than 2 Å following structural alignment of equivalent back bone atoms.

A method for designing a potential inhibitor of a DPPI or DPPI-like protein comprising the steps of:

• a) providing a three dimensional model of the receptor site in an enzyme with at least 37% amino acid sequence identity to the amino acid sequence of rat DPPI protein as shown in SEQ ID NO:
• 1 and a known inhibitor, b) locating the conserved residues in the known inhibitor which constitute the inhibition binding pocket, c) designing a new a DPPI or DPPI-like protein inhibitor, which possesses complementary structural features and binding forces to the residues in the known inhibitor's inhibition binding pocket.

A method according to any of claims 36-46, wherein said step of employing said structural co-ordinates to design, or select said potential inhibitor comprises the steps of:

• a) identifying chemical entities or fragments capable of associating with a protein with at least 37% amino acid sequence identity to the amino acid sequence of rat DPPI protein as shown in SEQ ID NO:
• 1, and b) assembling the identified chemical entities or fragments into a single 48. A chemical compound and/or potential inhibitor identified by a method according to any of claims 36-47.

A potential inhibitor, which possesses a positive charge that forms a salt bridge to the negative charge on the side chain of a conserved Asp1 and/or Asp274 of a protein with at least 37% amino acid sequence identity to the amino acid sequence of rat DPPI protein as shown in SEQ ID NO:

• 1