Crystallization of the Mycobacterium tuberculosis cell-division protein FtsZ

Mycobacterium tuberculosis FtsZ (MtbFtsZ), an essential protein in bacteria l cell division, has been crystallized in the presence of a new inhibitor o f MtbFtsZ polymerization and GTPase activity, ethyl (6-amino-2,3-dihydro-4- phenyl-1H-pyrido[4,3-b][1,4]diazepin-8-yl)-carbamate (SRI-7614). Crystals o f the MtbFtsZ-SRI-7614 complex (form I, 30% polyethylene glycol 4000, 0.1 M sodium citrate pH 5.6, 0.2 M NH4OAc, 293 K) belong to space group P6(1) or P6(5), with unit-cell parameters a = 88.78, c = 178.02 Angstrom, and diffr act to 2.3 Angstrom resolution. A second crystal form, of the GDP complex, grows in the presence or absence of Mg2+ from PEG 4000 at 277 K or from (NH 4)(2)SO4 at 293 K, respectively (form II, space group P6(2)22 or P6(4)22, w ith unit-cell parameters a = 135.02, c = 328.97 Angstrom or a = 129.30, c = 327.97 Angstrom, respectively). Complete data sets to similar to7 Angstrom resolution have been collected from both. Exceptional form II crystals dif fract to at least 4.5 Angstrom resolution. Determination of the MtbFtsZ str ucture may advance the design of improved inhibitors of FtsZ polymerization .