2R75

Aquifex aeolicus FtsZ with 8-morpholino-GTP

Summary for 2R75

• Entry DOI: 10.2210/pdb2r75/pdb
• Related: 2R6R
• Descriptor: Cell division protein ftsZ, MAGNESIUM ION, 8-morpholin-4-ylguanosine 5'-(tetrahydrogen triphosphate), ... (4 entities in total)
• Functional Keywords: gtpase, tubulin-like, inhibitor, cell cycle
• Biological source: Aquifex aeolicus
• Cellular location: Cytoplasm (By similarity): O66809
• Total number of polymer chains: 1
• Total formula weight: 37461.81

Authors

Lappchen, T.,Pinas, V.A.,Hartog, A.F.,Koomen, G.J.,Schaffner-Barbero, C.,Andreu, J.M.,Trambaiolo, D.,Lowe, J.,Juhem, A.,Popov, A.V.,den Blaauwen, T. (deposition date: 2007-09-07, release date: 2008-07-22, Last modification date: 2023-08-30)

Primary citation

Lappchen, T.,Pinas, V.A.,Hartog, A.F.,Koomen, G.J.,Schaffner-Barbero, C.,Andreu, J.M.,Trambaiolo, D.,Lowe, J.,Juhem, A.,Popov, A.V.,den Blaauwen, T.
Probing FtsZ and tubulin with C8-substituted GTP analogs reveals differences in their nucleotide binding sites
Chem.Biol., 15:189-199, 2008

PubMed Abstract: The cytoskeletal proteins, FtsZ and tubulin, play a pivotal role in prokaryotic cell division and eukaryotic chromosome segregation, respectively. Selective inhibitors of the GTP-dependent polymerization of FtsZ could constitute a new class of antibiotics, while several inhibitors of tubulin are widely used in antiproliferative therapy. In this work, we set out to identify selective inhibitors of FtsZ based on the structure of its natural ligand, GTP. We found that GTP analogs with small hydrophobic substituents at C8 of the nucleobase efficiently inhibit FtsZ polymerization, whereas they have an opposite effect on the polymerization of tubulin. The inhibitory activity of the GTP analogs on FtsZ polymerization allowed us to crystallize FtsZ in complex with C8-morpholino-GTP, revealing the binding mode of a GTP derivative containing a nonmodified triphosphate chain.

PubMed: 18291323
DOI: 10.1016/j.chembiol.2007.12.013

Experimental method

X-RAY DIFFRACTION (1.402 Å)