2YVP

Crystal structure of NDX2 in complex with MG2+ and ampcpr from thermus thermophilus HB8

Summary for 2YVP

• Entry DOI: 10.2210/pdb2yvp/pdb
• Related: 2YVM 2YVN 2YVO
• Descriptor: MutT/nudix family protein, MAGNESIUM ION, METHYLENE ADP-BETA-XYLOSE, ... (4 entities in total)
• Functional Keywords: nudix protein, adp-ribose, fad, thermus thermophilus, hydrolase, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi
• Biological source: Thermus thermophilus
• Total number of polymer chains: 1
• Total formula weight: 20966.70

Authors

Wakamatsu, T.,Nakagawa, N.,Kuramitsu, S.,Yokoyama, S.,Masui, R.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-04-13, release date: 2008-02-26, Last modification date: 2023-10-25)

Primary citation

Wakamatsu, T.,Nakagawa, N.,Kuramitsu, S.,Masui, R.
Structural basis for different substrate specificities of two ADP-ribose pyrophosphatases from Thermus thermophilus HB8
J.Bacteriol., 190:1108-1117, 2008

PubMed Abstract: ADP-ribose (ADPR) is one of the main substrates of Nudix proteins. Among the eight Nudix proteins of Thermus thermophilus HB8, we previously determined the crystal structure of Ndx4, an ADPR pyrophosphatase (ADPRase). In this study we show that Ndx2 of T. thermophilus also preferentially hydrolyzes ADPR and flavin adenine dinucleotide and have determined its crystal structure. We have determined the structures of Ndx2 alone and in complex with Mg2+, with Mg2+ and AMP, and with Mg2+ and a nonhydrolyzable ADPR analogue. Although Ndx2 recognizes the AMP moiety in a manner similar to those for other ADPRases, it recognizes the terminal ribose in a distinct manner. The residues responsible for the recognition of the substrate in Ndx2 are not conserved among ADPRases. This may reflect the diversity in substrate specificity among ADPRases. Based on these results, we propose the classification of ADPRases into two types: ADPRase-I enzymes, which exhibit high specificity for ADPR; and ADPRase-II enzymes, which exhibit low specificity for ADPR. In the active site of the ternary complexes, three Mg2+ ions are coordinated to the side chains of conserved glutamate residues and water molecules. Substitution of Glu90 and Glu94 with glutamine suggests that these residues are essential for catalysis. These results suggest that ADPRase-I and ADPRase-II enzymes have nearly identical catalytic mechanisms but different mechanisms of substrate recognition.

PubMed: 18039767
DOI: 10.1128/JB.01522-07

Experimental method

X-RAY DIFFRACTION (1.66 Å)