5CB5

Structural Insights into the Mechanism of Escherichia coli Ymdb

Summary for 5CB5

• Entry DOI: 10.2210/pdb5cb5/pdb
• Related: 5CB3
• Descriptor: O-acetyl-ADP-ribose deacetylase, ADENOSINE-5-DIPHOSPHORIBOSE, SULFATE ION, ... (6 entities in total)
• Functional Keywords: deacetylase, adpr, oaadpr, macro domain, hydrolase
• Biological source: Escherichia coli K12
• Total number of polymer chains: 18
• Total formula weight: 365599.19

Authors

Zhang, W.,Wang, C.,Song, Y.,Shao, C.,Zhang, X.,Zang, J. (deposition date: 2015-06-30, release date: 2015-11-04, Last modification date: 2023-11-08)

Primary citation

Zhang, W.,Wang, C.,Song, Y.,Shao, C.,Zhang, X.,Zang, J.
Structural insights into the mechanism of Escherichia coli YmdB: A 2'-O-acetyl-ADP-ribose deacetylase
J.Struct.Biol., 192:478-486, 2015

PubMed 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.

PubMed: 26481419
DOI: 10.1016/j.jsb.2015.10.010

Experimental method

X-RAY DIFFRACTION (2.8 Å)