6CZ6

Mycobacterium tuberculosis transcriptional regulator

Summary for 6CZ6

• Entry DOI: 10.2210/pdb6cz6/pdb
• Related: 6CYJ 6CYY 6D2S
• Descriptor: HTH-type transcriptional regulator PrpR, COENZYME A, IRON/SULFUR CLUSTER, ... (4 entities in total)
• Functional Keywords: transcription, regulator, dna binding protein
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 196727.99

Authors

Tang, S.,Sacchettini, J. (deposition date: 2018-04-08, release date: 2019-04-17, Last modification date: 2024-10-16)

Primary citation

Tang, S.,Hicks, N.D.,Cheng, Y.S.,Silva, A.,Fortune, S.M.,Sacchettini, J.C.
Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor.
Nucleic Acids Res., 47:9934-9949, 2019

PubMed Abstract: The pathogenicity of Mycobacterium tuberculosis depends upon its ability to catabolize host cholesterol. Upregulation of the methylcitrate cycle (MCC) is required to assimilate and detoxify propionyl-CoA, a cholesterol degradation product. The transcription of key genes prpC and prpD in MCC is activated by MtPrpR, a member of a family of prokaryotic transcription factors whose structures and modes of action have not been clearly defined. We show that MtPrpR has a novel overall structure and directly binds to CoA or short-chain acyl-CoA derivatives to form a homotetramer that covers the binding cavity and locks CoA tightly inside the protein. The regulation of this process involves a [4Fe4S] cluster located close to the CoA-binding cavity on a neighboring chain. Mutations in the [4Fe4S] cluster binding residues rendered MtPrpR incapable of regulating MCC gene transcription. The structure of MtPrpR without the [4Fe4S] cluster-binding region shows a conformational change that prohibits CoA binding. The stability of this cluster means it is unlikely a redox sensor but may function by sensing ambient iron levels. These results provide mechanistic insights into this family of critical transcription factors who share similar structures and regulate gene transcription using a combination of acyl-CoAs and [4Fe4S] cluster.

PubMed: 31504787
DOI: 10.1093/nar/gkz724

Experimental method

X-RAY DIFFRACTION (2.7 Å)