3LA3

Crystal structure of NtcA in complex with 2,2-difluoropentanedioic acid

Summary for 3LA3

• Entry DOI: 10.2210/pdb3la3/pdb
• Related: 3LA2 3LA7
• Descriptor: Global nitrogen regulator, 2,2-difluoropentanedioic acid (3 entities in total)
• Functional Keywords: nitrogen regulator, activator, dna-binding, transcription, transcription regulation
• Biological source: Anabaena
• Total number of polymer chains: 2
• Total formula weight: 54581.48

Authors

Zhao, M.X.,Jiang, Y.L.,He, Y.X.,Chen, Y.F.,Teng, Y.B.,Chen, Y.X.,Zhang, C.C.,Zhou, C.Z. (deposition date: 2010-01-06, release date: 2010-07-14, Last modification date: 2024-03-20)

Primary citation

Zhao, M.X.,Jiang, Y.L.,He, Y.X.,Chen, Y.F.,Teng, Y.B.,Chen, Y.X.,Zhang, C.C.,Zhou, C.Z.
Structural basis for the allosteric control of the global transcription factor NtcA by the nitrogen starvation signal 2-oxoglutarate.
Proc.Natl.Acad.Sci.USA, 107:12487-12492, 2010

PubMed Abstract: 2-oxogluatarate (2-OG), a metabolite of the highly conserved Krebs cycle, not only plays a critical role in metabolism, but also constitutes a signaling molecule in a variety of organisms ranging from bacteria to plants and animals. In cyanobacteria, the accumulation of 2-OG constitutes the signal of nitrogen starvation and NtcA, a global transcription factor, has been proposed as a putative receptor for 2-OG. Here we present three crystal structures of NtcA from the cyanobacterium Anabaena: the apoform, and two ligand-bound forms in complex with either 2-OG or its analogue 2,2-difluoropentanedioic acid. All structures assemble as homodimers, with each subunit composed of an N-terminal effector-binding domain and a C-terminal DNA-binding domain connected by a long helix (C-helix). The 2-OG binds to the effector-binding domain at a pocket similar to that used by cAMP in catabolite activator protein, but with a different pattern. Comparative structural analysis reveals a putative signal transmission route upon 2-OG binding. A tighter coiled-coil conformation of the two C-helices induced by 2-OG is crucial to maintain the proper distance between the two F-helices for DNA recognition. Whereas catabolite activator protein adopts a transition from off-to-on state upon cAMP binding, our structural analysis explains well why NtcA can bind to DNA even in its apoform, and how 2-OG just enhances the DNA-binding activity of NtcA. These findings provided the structural insights into the function of a global transcription factor regulated by 2-OG, a metabolite standing at a crossroad between carbon and nitrogen metabolisms.

PubMed: 20616047
DOI: 10.1073/pnas.1001556107

Experimental method

X-RAY DIFFRACTION (2.4 Å)