Crystallization of the Mycobacterium tuberculosis cell-division protein FtsZ.
Mycobacterium tuberculosis FtsZ (MtbFtsZ), an essential protein in bacterial cell division, has been crystallized in the presence of a new inhibitor of 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 of the MtbFtsZ-SRI-7614 complex (form I, 30% polyethylene glycol 4000, 0.1 M sodium citrate pH 5.6, 0.2 M NH(4)OAc, 293 K) belong to space group P6(1) or P6(5), with unit-cell parameters a = 88.78, c = 178. 02 A, and diffract to 2.3 A resolution. A second crystal form, of the GDP complex, grows in the presence or absence of Mg(2+) from PEG 4000 at 277 K or from (NH(4))(2)SO(4) at 293 K, respectively (form II, space group P6(2)22 or P6(4)22, with unit-cell parameters a = 135.02, c = 328.97 A or a = 129.30, c = 327.97 A, respectively). Complete data sets to approximately 7 A resolution have been collected from both. Exceptional form II crystals diffract to at least 4.5 A resolution. Determination of the MtbFtsZ structure may advance the design of improved inhibitors of FtsZ polymerization.
Leung
A K
AK
Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, USA.
White
E L
EL
Ross
L J
LJ
Borhani
D W
DW
D001381:Azepines / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry; D003460:Crystallization; D003598:Cytoskeletal Proteins; D009169:Mycobacterium tuberculosis / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry; D011487:Protein Conformation; D014961:X-Ray Diffraction
D001381:Azepines; D001426:Bacterial Proteins; D002219:Carbamates; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D009711:Nucleotides; C418468:SRI 7614