4QB9

Crystal structure of Mycobacterium smegmatis Eis in complex with paromomycin

Summary for 4QB9

• Entry DOI: 10.2210/pdb4qb9/pdb
• Descriptor: Enhanced intracellular survival protein, PAROMOMYCIN, SULFATE ION (3 entities in total)
• Functional Keywords: gnat fold, scp fold, acetyltransferase, transferase
• Biological source: Mycobacterium smegmatis
• Total number of polymer chains: 6
• Total formula weight: 281072.23

Authors

Kim, K.H.,Ahn, D.R.,Yoon, H.J.,Yang, J.K.,Suh, S.W. (deposition date: 2014-05-06, release date: 2015-04-01, Last modification date: 2024-03-20)

Primary citation

Kim, K.H.,An, D.R.,Yoon, H.J.,Yang, J.K.,Suh, S.W.
Structure of Mycobacterium smegmatis Eis in complex with paromomycin.
Acta Crystallogr.,Sect.F, 70:1173-1179, 2014

PubMed Abstract: The Rv2416c gene of Mycobacterium tuberculosis (Mtb) encodes the enhanced intracellular survival (Eis) protein that enhances intracellular survival of the pathogen in host macrophages during infection. The Mtb Eis protein is released into the cytoplasm of the phagocyte during intracellular infection and modulates the host immune response. It also contributes to drug resistance by acetylating multiple amine groups of aminoglycosides. Interestingly, the nonpathogenic M. smegmatis (Msm) contains a homologous eis gene (MSMEG_3513). The overall structures of Mtb Eis and Msm Eis are highly similar to each other, reflecting the high level (58%) of amino-acid sequence identity between them. Both Mtb Eis and Msm Eis are active as aminoglycoside acetyltransferases, while only Mtb Eis functions as an N(ℇ)-acetyltransferase to acetylate Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase 7 (MKP-7), leading to the suppression of host immune responses. Here, the crystal structure of Msm Eis in the paromomycin-bound form is reported, revealing detailed interactions between an aminoglycoside antibiotic and Msm Eis. The crystal structure of Msm Eis in the paromomycin-bound form has been determined at 3.3 Å resolution. This work provides potentially useful information for structure-guided discovery of Eis inhibitors as a novel antituberculosis drug against drug-resistant Mtb.

PubMed: 25195887
DOI: 10.1107/S2053230X14017385

Experimental method

X-RAY DIFFRACTION (3.293 Å)