Structural insights into the mechanism of Escherichia coli YmdB: A 2′-O-acetyl-ADP-ribose deacetylase

Structural insights into the mechanism of Escherichia coli YmdB: A 2′-O-acetyl-ADP-ribose... The Escherichia coli protein YmdB belongs to the macrodomain protein family, which can bind ADP-ribose (ADPr) and its derivatives. Recently, YmdB was reported to be capable of deacetylating O-acetyl-ADP-ribose (OAADPr) to yield ADPr and free acetate. To study the substrate specificity and catalytic mechanism, the crystal structures of E. coli YmdB in complex with ADPr, double mutant N25AD35A complexed with 2′-OAADPr, and Y126A/ADPr complex were solved at 1.8Å, 2.8Å and 3.0Å resolution, respectively. Structural and biochemical studies reveal that YmdB has substrate specificity against 2′-OAADPr. The conserved residues Asn25 and Asp35 are crucial for catalytic activity, and an active water molecule is proposed as the nucleophile to attack the acetyl group of 2′-OAADPr. Our findings indicate that the conserved phenyl group of Tyr126 plays a crucial role in catalytic activity by stabilizing the right orientation of distal ribose and that Gly32 may be important for activity by interacting with the acetyl group of 2′-OAADPr. Based on these observations, a model of YmdB in complex with 2′-OAADPr was made to illustrate the proposed catalytic mechanism of YmdB. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Structural Biology Elsevier

Structural insights into the mechanism of Escherichia coli YmdB: A 2′-O-acetyl-ADP-ribose deacetylase

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Inc.
ISSN
1047-8477
eISSN
1095-8657
D.O.I.
10.1016/j.jsb.2015.10.010
Publisher site
See Article on Publisher Site

Abstract

The Escherichia coli protein YmdB belongs to the macrodomain protein family, which can bind ADP-ribose (ADPr) and its derivatives. Recently, YmdB was reported to be capable of deacetylating O-acetyl-ADP-ribose (OAADPr) to yield ADPr and free acetate. To study the substrate specificity and catalytic mechanism, the crystal structures of E. coli YmdB in complex with ADPr, double mutant N25AD35A complexed with 2′-OAADPr, and Y126A/ADPr complex were solved at 1.8Å, 2.8Å and 3.0Å resolution, respectively. Structural and biochemical studies reveal that YmdB has substrate specificity against 2′-OAADPr. The conserved residues Asn25 and Asp35 are crucial for catalytic activity, and an active water molecule is proposed as the nucleophile to attack the acetyl group of 2′-OAADPr. Our findings indicate that the conserved phenyl group of Tyr126 plays a crucial role in catalytic activity by stabilizing the right orientation of distal ribose and that Gly32 may be important for activity by interacting with the acetyl group of 2′-OAADPr. Based on these observations, a model of YmdB in complex with 2′-OAADPr was made to illustrate the proposed catalytic mechanism of YmdB.

Journal

Journal of Structural BiologyElsevier

Published: Dec 1, 2015

References

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