5i8u

Crystal Structure of the RV1700 (MT ADPRASE) E142Q mutant

spinqualitylabelsall models 5i8u, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5i8u is a 7 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: FMT, NA, PEG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ADPP_MYCTU Catalyzes the hydrolysis of ADP-ribose (ADPR) to AMP and ribose-5-phosphate. Can also hydrolyze ADP-mannose and ADP-glucose, with lower efficiency. Has weaker activity with NAD, GDP-sugars and UDP-sugars (PubMed:27683242). Also catalyzes the conversion of 8-oxo-dGDP to 8-oxo-dGMP, and 8-oxo-GDP to 8-oxo-GMP. Functions in concert with MutT1 to detoxify 8-oxo-dGTP to 8-oxo-dGMP and may play an important role in supporting cellular growth under oxidative stress (PubMed:23463507). The catalytic efficiency is much higher for the hydrolysis of ADPR than 8-oxo-dGTP, suggesting a more relevant biological role in hydrolysis of ADPR (PubMed:27683242). Publication Abstract from PubMed Mycobacterium tuberculosis represents one of the world's most devastating infectious agents - with one third of the world's population infected and 1.5 million people dying each year from this deadly pathogen. As part of an effort to identify targets for therapeutic intervention, we carried out the kinetic characterization of the product of gene rv1700 of M. tuberculosis. Based on its sequence and its structure, the protein had been tentatively identified as a pyrophosphohydrolase specific for adenosine diphosphate ribose (ADPR), a compound involved in various pathways including oxidative stress response and tellurite resistance. In this work we carry out a kinetic, mutational and structural investigation of the enzyme, which provides a full characterization of this Mt-ADPRase. Optimal catalytic rates were achieved at alkaline pH (7.5-8.5) with either 0.5-1 mM Mg2+ or 0.02-1 mM Mn2+. K m and k cat values for hydrolysis of ADPR with Mg2+ ions are 200 +/- 19 muM and 14.4 +/- 0.4 s-1, and with Mn2+ ions are 554 +/- 64 muM and 28.9 +/- 1.4 s-1. Four residues proposed to be important in the catalytic mechanism of the enzyme were individually mutated and the kinetics of the mutant enzymes were characterized. In the four cases, the K m increased only slightly (2- to 3-fold) but the k cat decreased significantly (300- to 1900-fold), confirming the participation of these residues in catalysis. An analysis of the sequence and structure conservation patterns in Nudix ADPRases permits an unambiguous identification of members of the family and provides insight into residues involved in catalysis and their participation in substrate recognition in the Mt-ADPRase. Kinetic and mutational studies of the adenosine diphosphate ribose hydrolase from Mycobacterium tuberculosis.,O'Handley SF, Thirawatananond P, Kang LW, Cunningham JE, Leyva JA, Amzel LM, Gabelli SB J Bioenerg Biomembr. 2016 Sep 28. PMID:27683242 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ADP-ribose pyrophosphatase 3D structures

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