5XE8

Crystal Structure of the Peptidase Domain of Streptococcus mutans ComA

Summary for 5XE8

• Entry DOI: 10.2210/pdb5xe8/pdb
• Related: 5XE9
• Descriptor: Putative ABC transporter, ATP-binding protein ComA, DI(HYDROXYETHYL)ETHER (3 entities in total)
• Functional Keywords: peptidase, quorum-sensing, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Streptococcus mutans serotype c
• Total number of polymer chains: 2
• Total formula weight: 34919.89

Authors

Ishii, S.,Fukui, K.,Yokoshima, S.,Kumagai, K.,Beniyama, Y.,Kodama, T.,Fukuyama, T.,Okabe, T.,Nagano, T.,Kojima, H.,Yano, T. (deposition date: 2017-04-03, release date: 2017-06-28, Last modification date: 2023-11-22)

Primary citation

Ishii, S.,Fukui, K.,Yokoshima, S.,Kumagai, K.,Beniyama, Y.,Kodama, T.,Fukuyama, T.,Okabe, T.,Nagano, T.,Kojima, H.,Yano, T.
High-throughput Screening of Small Molecule Inhibitors of the Streptococcus Quorum-sensing Signal Pathway
Sci Rep, 7:4029-4029, 2017

PubMed Abstract: The main components of the quorum-sensing system are expected to be favorable targets for drug development to combat various chronic infectious diseases. ComA of Streptococcus is an ATP-binding cassette transporter containing a peptidase domain (PEP), which is essential for the quorum-sensing signal production. Using high-throughput screening, we found a potent small molecule that suppressed the S. mutans quorum-sensing pathway through inhibition of PEP activity. The compound effectively attenuated the biofilm formation and competence development of S. mutans without inhibiting cell growth. The kinetic and structural studies with this molecule and a related compound unexpectedly revealed an allosteric site of PEP. This relatively hydrophobic site is thought to undergo large structural changes during the catalytic process. These compounds inhibit PEP activity by binding to and suppressing the structural changes of this site. These results showed that PEP is a good target for inhibitors of the Streptococcus quorum-sensing system.

PubMed: 28642545
DOI: 10.1038/s41598-017-03567-2

Experimental method

X-RAY DIFFRACTION (3.1 Å)