2dsc
From Proteopedia
(New page: 200px<br /> <applet load="2dsc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dsc, resolution 2.00Å" /> '''Crystal structure o...) |
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caption="2dsc, resolution 2.00Å" /> | caption="2dsc, resolution 2.00Å" /> | ||
'''Crystal structure of human ADP-ribose pyrophosphatase NUDT5 in complex with magnesium and ADP-ribose'''<br /> | '''Crystal structure of human ADP-ribose pyrophosphatase NUDT5 in complex with magnesium and ADP-ribose'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging | + | Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report here the crystal structures of hNUDT5 in apo form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogen-bonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on APnA, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA. |
==About this Structure== | ==About this Structure== | ||
| - | 2DSC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and APR as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2DSC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=APR:'>APR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DSC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: nudt5]] | [[Category: nudt5]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:02:05 2008'' |
Revision as of 15:02, 21 February 2008
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Crystal structure of human ADP-ribose pyrophosphatase NUDT5 in complex with magnesium and ADP-ribose
Overview
Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report here the crystal structures of hNUDT5 in apo form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogen-bonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on APnA, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA.
About this Structure
2DSC is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity., Zha M, Zhong C, Peng Y, Hu H, Ding J, J Mol Biol. 2006 Dec 15;364(5):1021-33. Epub 2006 Oct 3. PMID:17052728
Page seeded by OCA on Thu Feb 21 17:02:05 2008
Categories: Homo sapiens | Single protein | Ding, J. | Zha, M. | Zhong, C. | APR | MG | Adp-ribose pyrophosphatase | Adpr | Nudix domain | Nudt5
