Crystalline composition of farsenyl pyrophosphate synthase (IspA)
Provided are crystals relating to Farsenyl Pvrophosphate Synthase (IspA) from E. coli and its various uses.
1. A composition comprising a protein, isopentyl pyrophosphate and Risedronate complex in co-crystalline form, wherein the protein of the complex consists of residues 1-314 of SEQ ID NO: 1, wherein said protein is in complex with isopentyl pyrophosphate and Risedronate, and wherein the co-crystal has a crystal lattice in a P4 1 22 space group and unit cell dimensions, +/−5%, of a=88.80 Å b=88.80 Å and c=174.99 Å, α=β=γ=90°.
2. The composition according to claim 1 wherein the co-crystal diffracts X-rays for a determination of structure coordinates to a resolution of a value equal to or less than 3.0 Å.
3. A method for forming a co-crystal of a protein, isopentyl pyrophosphate and Risedronate comprising:
forming a crystallization volume comprising a precipitant solution, isopentyl pyrophosphate, Risedronate and a protein that consists of residues 1-314 of SEQ ID NO: 1, wherein said protein is in complex with isopentyl pyrophosphate and Risedronate; and
storing the crystallization volume under conditions suitable for formation of a protein, isopentyl pyrophosphate and Risedronate complex co-crystal, wherein the co-crystal has a crystal lattice in a P4 1 22 space group and unit cell dimensions, +/−5%, of a=88.80 Å, b=88.80 Å and c=174.99 Å, α=β=γ=90°.
4. The method according to claim 3 wherein the co-crystal diffracts X-rays for a determination of structure coordinates to a resolution of a value equal to or less than 3.0 Å.
5. A method of solving a structure of a protein comprising:
forming a crystallization volume comprising a precipitant solution, isopentyl pyrophosphate, Risedronate and a protein that consists of residues 1-314 of SEQ ID NO: 1, wherein said protein is in complex with isopentyl pyrophosphate and Risedronate;
storing the crystallization volume under conditions suitable for formation of a protein, isopentyl pyrophosphate and Risedronate complex co-crystal, wherein the co-crystal has a crystal lattice in a P4 1 22 space group and unit cell dimensions, +/−5%, of a=88.80 Å, b=88.80 Å and c=174.99 Å, α=β=γ=90°;
diffracting the co-crystal to produce a diffraction pattern; and
solving the structure of the protein from the diffraction pattern.
6. A non-crystalline protein consisting of residues 1-314 of SEQ ID NO: 1.
7. A method of identifying an entity that potentially associates with a protein comprising:
forming a crystallization volume comprising a precipitant solution, isopentyl pyrophosphate, Risedronate and a protein that consists of residues 1-314 of SEQ ID NO: 1, wherein said protein is in complex with isopentyl pyrophosphate and Risedronate;
storing the crystallization volume under conditions suitable for formation of a protein, isopentyl pyrophosphate and Risedronate complex co-crystal, wherein the co-crystal has a crystal lattice in a P4 1 22 space group and unit cell dimensions, +/−5%, of a=88.80 Å b=88.80 Å and c=174.99 Å, α=β=γ=90°;
diffracting the co-crystal to produce a diffraction pattern;
solving the structure of the protein from the diffraction pattern;
performing rational drug design using the solved structure; and
identifying an entity that associates with the protein.
8. The method according to claim 7 further comprising selecting one or more entities based on the rational drug design and contacting the selected entities with the protein.
9. The method according to claim 8 further comprising measuring an activity of the protein when contacted with the one or more entities.
10. An isolated non-crystalline protein consisting of residues 1-314 of SEQ ID NO: 1.