First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.

3ac9

From Proteopedia

Jump to: navigation, search
3ac9, resolution 2.10Å ()
Ligands: ,
Gene: NUDT5, HSPC115 (Homo sapiens)
Activity: ADP-ribose diphosphatase, with EC number 3.6.1.13
Related: 3l85, 3aca


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal structure of human NUDT5 complexed with 8-oxo-dGDP and manganese

Publication Abstract from PubMed

Human NUDT5 (hNUDT5) hydrolyzes various modified nucleoside diphosphates including 8-oxo-dGDP, 8-oxo-dADP and ADP-ribose (ADPR). However, the structural basis of the broad substrate specificity remains unknown. Here, we report the crystal structures of hNUDT5 complexed with 8-oxo-dGDP and 8-oxo-dADP. These structures reveal an unusually different substrate-binding mode. In particular, the positions of two phosphates (alpha and beta phosphates) of substrate in the 8-oxo-dGDP and 8-oxo-dADP complexes are completely inverted compared with those in the previously reported hNUDT5-ADPR complex structure. This result suggests that the nucleophilic substitution sites of the substrates involved in hydrolysis reactions differ despite the similarities in the chemical structures of the substrates and products. To clarify this hypothesis, we employed the isotope-labeling method and revealed that 8-oxo-dGDP is attacked by nucleophilic water at Pbeta, whereas ADPR is attacked at Palpha. This observation reveals that the broad substrate specificity of hNUDT5 is achieved by a diversity of not only substrate recognition, but also hydrolysis mechanisms and leads to a novel aspect that enzymes do not always catalyze the reaction of substrates with similar chemical structures by using the chemically equivalent reaction site.

Diverse substrate recognition and hydrolysis mechanisms of human NUDT5., Arimori T, Tamaoki H, Nakamura T, Kamiya H, Ikemizu S, Takagi Y, Ishibashi T, Harashima H, Sekiguchi M, Yamagata Y, Nucleic Acids Res. 2011 Nov 1;39(20):8972-83. Epub 2011 Jul 17. PMID:21768126

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Function

[NUDT5_HUMAN] Hydrolyzes with similar activities ADP-ribose ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze other nucleotide sugars with low activity.[1]

About this Structure

3ac9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Arimori T, Tamaoki H, Nakamura T, Kamiya H, Ikemizu S, Takagi Y, Ishibashi T, Harashima H, Sekiguchi M, Yamagata Y. Diverse substrate recognition and hydrolysis mechanisms of human NUDT5. Nucleic Acids Res. 2011 Nov 1;39(20):8972-83. Epub 2011 Jul 17. PMID:21768126 doi:10.1093/nar/gkr575
  1. Zha M, Zhong C, Peng Y, Hu H, Ding J. Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity. J Mol Biol. 2006 Dec 15;364(5):1021-33. Epub 2006 Oct 3. PMID:17052728 doi:10.1016/j.jmb.2006.09.078

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools