5H04

Crystal structure of an ADP-ribosylating toxin BECa of a novel binary enterotoxin of C. perfringens with NADH

Summary for 5H04

• Entry DOI: 10.2210/pdb5h04/pdb
• Related: 5H03
• Descriptor: Binary enterotoxin of Clostridium perfringens component a, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: toxin, adp-ribosyltransferase
• Biological source: Clostridium perfringens
• Total number of polymer chains: 1
• Total formula weight: 48192.75

Authors

Kawahara, K.,Yonogi, S.,Munetomo, R.,Oki, H.,Yoshida, T.,Ohkubo, T.,Kumeda, Y.,Matsuda, S.,Kodama, T.,Iida, T.,Nakamura, S. (deposition date: 2016-10-03, release date: 2016-11-02, Last modification date: 2023-11-08)

Primary citation

Kawahara, K.,Yonogi, S.,Munetomo, R.,Oki, H.,Yoshida, T.,Kumeda, Y.,Matsuda, S.,Kodama, T.,Ohkubo, T.,Iida, T.,Nakamura, S.
Crystal structure of the ADP-ribosylating component of BEC, the binary enterotoxin of Clostridium perfringens.
Biochem.Biophys.Res.Commun., 480:261-267, 2016

PubMed Abstract: Binary enterotoxin of Clostridium perfringens (BEC), consisting of the components BECa and BECb, was recently identified as a novel enterotoxin produced by C. perfringens that causes acute gastroenteritis in humans. Although the detailed mechanism of cell intoxication by BEC remains to be defined, BECa shows both NAD-glycohydrolase and actin ADP-ribosyltransferase activities in the presence of NAD. In this study, we determined the first crystal structure of BECa in its apo-state and in complex with NADH. The structure of BECa shows striking resemblance with other binary actin ADP-ribosylating toxins (ADPRTs), especially in terms of its overall protein fold and mechanisms of substrate recognition. We present a detailed picture of interactions between BECa and NADH, including bound water molecules located near the C1'-N glycosidic bond of NADH and the catalytically important ADP-ribosylating turn-turn (ARTT) loop. We observed that the conformational rearrangement of the ARTT loop, possibly triggered by a conformational change involving a conserved tyrosine residue coupled with substrate binding, plays a crucial role in catalysis by properly positioning a catalytic glutamate residue in the E-X-E motif of the ARTT loop in contact with the nucleophile. Our results for BECa provide insight into the common catalytic mechanism of the family of binary actin ADPRTs.

PubMed: 27751850
DOI: 10.1016/j.bbrc.2016.10.042

Experimental method

X-RAY DIFFRACTION (1.825 Å)