5DQV

The crystal structure of Bacillus subtilis YpgQ

Summary for 5DQV

• Entry DOI: 10.2210/pdb5dqv/pdb
• Related: 5DQW
• Descriptor: Uncharacterized protein, NICKEL (II) ION (3 entities in total)
• Functional Keywords: hd domain, hydrolase
• Biological source: Bacillus subtilis
• Total number of polymer chains: 2
• Total formula weight: 47431.04

Authors

Jeon, Y.J.,Song, W.S.,Yoon, S.I. (deposition date: 2015-09-15, release date: 2016-04-27, Last modification date: 2024-03-20)

Primary citation

Jeon, Y.J.,Park, S.C.,Song, W.S.,Kim, O.H.,Oh, B.C.,Yoon, S.I.
Structural and biochemical characterization of bacterial YpgQ protein reveals a metal-dependent nucleotide pyrophosphohydrolase
J.Struct.Biol., 195:113-122, 2016

PubMed Abstract: The optimal balance of cellular nucleotides and the efficient elimination of non-canonical nucleotides are critical to avoiding erroneous mutation during DNA replication. One such mechanism involves the degradation of excessive or abnormal nucleotides by nucleotide-hydrolyzing enzymes. YpgQ contains the histidine-aspartate (HD) domain that is involved in the hydrolysis of nucleotides or nucleic acids, but the enzymatic activity and substrate specificity of YpgQ have never been characterized. Here, we unravel the catalytic activity and structural features of YpgQ to report the first Mn(2+)-dependent pyrophosphohydrolase that hydrolyzes (deoxy)ribonucleoside triphosphate [(d)NTP] to (deoxy)ribonucleoside monophosphate and pyrophosphate using the HD domain. YpgQ from Bacillus subtilis (bsYpgQ) displays a helical structure and assembles into a unique dimeric architecture that has not been observed in other HD domain-containing proteins. Each bsYpgQ monomer accommodates a metal ion and a nucleotide substrate in a cavity located between the N- and C-terminal lobes. The metal cofactor is coordinated by the canonical residues of the HD domain, namely, two histidine residues and two aspartate residues, and is positioned in close proximity to the β-phosphate group of the nucleotide, allowing us to propose a nucleophilic attack mechanism for the nucleotide hydrolysis reaction. YpgQ enzymes from other bacterial species also catalyze pyrophosphohydrolysis but exhibit different substrate specificity. Comparative structural and mutational studies demonstrated that residues outside the major substrate-binding site of bsYpgQ are responsible for the species-specific substrate preference. Taken together, our structural and biochemical analyses highlight the substrate-recognition mode and catalysis mechanism of YpgQ in pyrophosphohydrolysis.

PubMed: 27062940
DOI: 10.1016/j.jsb.2016.04.002

Experimental method

X-RAY DIFFRACTION (2 Å)