5CET

Crystal structure of Rv2837c

Summary for 5CET

• Entry DOI: 10.2210/pdb5cet/pdb
• Related: 5CEU
• Descriptor: Bifunctional oligoribonuclease and PAP phosphatase NrnA, MANGANESE (II) ION (3 entities in total)
• Functional Keywords: phosphodiesterase, c-di-amp, mycobacterium tuberculosis, hydrolase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 1
• Total formula weight: 35979.70

Authors

Wang, F.,He, Q.,Zhu, D.,Liu, S.,Gu, L. (deposition date: 2015-07-07, release date: 2015-12-23, Last modification date: 2024-03-20)

Primary citation

He, Q.,Wang, F.,Liu, S.,Zhu, D.,Cong, H.,Gao, F.,Li, B.,Wang, H.,Lin, Z.,Liao, J.,Gu, L.
Structural and Biochemical Insight into the Mechanism of Rv2837c from Mycobacterium tuberculosis as a c-di-NMP Phosphodiesterase
J.Biol.Chem., 291:3668-3681, 2016

PubMed Abstract: The intracellular infections of Mycobacterium tuberculosis, which is the causative agent of tuberculosis, are regulated by many cyclic dinucleotide signaling. Rv2837c from M. tuberculosis is a soluble, stand-alone DHH-DHHA1 domain phosphodiesterase that down-regulates c-di-AMP through catalytic degradation and plays an important role in M. tuberculosis infections. Here, we report the crystal structure of Rv2837c (2.0 Å), and its complex with hydrolysis intermediate 5'-pApA (2.35 Å). Our structures indicate that both DHH and DHHA1 domains are essential for c-di-AMP degradation. Further structural analysis shows that Rv2837c does not distinguish adenine from guanine, which explains why Rv2837c hydrolyzes all linear dinucleotides with almost the same efficiency. We observed that Rv2837c degraded other c-di-NMPs at a lower rate than it did on c-di-AMP. Nevertheless, our data also showed that Rv2837c significantly decreases concentrations of both c-di-AMP and c-di-GMP in vivo. Our results suggest that beside its major role in c-di-AMP degradation Rv2837c could also regulate c-di-GMP signaling pathways in bacterial cell.

PubMed: 26668313
DOI: 10.1074/jbc.M115.699801

Experimental method

X-RAY DIFFRACTION (2 Å)