Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

5HV6

The ATP binding domain of rifampin phosphotransferase from Listeria monocytogenes

Summary for 5HV6
Entry DOI10.2210/pdb5hv6/pdb
Related5HV1 5HV2 5HV3
DescriptorPhosphoenolpyruvate synthase (2 entities in total)
Functional Keywordsantibiotic resistance, rifampin, phosphotransferase, transferase
Biological sourceListeria monocytogenes
Total number of polymer chains2
Total formula weight72732.84
Authors
Zhang, P.,Qi, X. (deposition date: 2016-01-28, release date: 2016-03-30, Last modification date: 2024-11-06)
Primary citationQi, X.,Lin, W.,Ma, M.,Wang, C.,He, Y.,He, N.,Gao, J.,Zhou, H.,Xiao, Y.,Wang, Y.,Zhang, P.
Structural basis of rifampin inactivation by rifampin phosphotransferase
Proc.Natl.Acad.Sci.USA, 113:3803-3808, 2016
Cited by
PubMed Abstract: Rifampin (RIF) is a first-line drug used for the treatment of tuberculosis and other bacterial infections. Various RIF resistance mechanisms have been reported, and recently an RIF-inactivation enzyme, RIF phosphotransferase (RPH), was reported to phosphorylate RIF at its C21 hydroxyl at the cost of ATP. However, the underlying molecular mechanism remained unknown. Here, we solve the structures of RPH from Listeria monocytogenes (LmRPH) in different conformations. LmRPH comprises three domains: an ATP-binding domain (AD), an RIF-binding domain (RD), and a catalytic His-containing domain (HD). Structural analyses reveal that the C-terminal HD can swing between the AD and RD, like a toggle switch, to transfer phosphate. In addition to its catalytic role, the HD can bind to the AD and induce conformational changes that stabilize ATP binding, and the binding of the HD to the RD is required for the formation of the RIF-binding pocket. A line of hydrophobic residues forms the RIF-binding pocket and interacts with the 1-amino, 2-naphthol, 4-sulfonic acid and naphthol moieties of RIF. The R group of RIF points toward the outside of the pocket, explaining the low substrate selectivity of RPH. Four residues near the C21 hydroxyl of RIF, His825, Arg666, Lys670, and Gln337, were found to play essential roles in the phosphorylation of RIF; among these the His825 residue may function as the phosphate acceptor and donor. Our study reveals the molecular mechanism of RIF phosphorylation catalyzed by RPH and will guide the development of a new generation of rifamycins.
PubMed: 27001859
DOI: 10.1073/pnas.1523614113
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.005 Å)
Structure validation

239803

数据于2025-08-06公开中

PDB statisticsPDBj update infoContact PDBjnumon