5fud | pdb_00005fud

Oceanobacillus iheyensis macrodomain with MES bound

spinqualitylabelsall models 5fud, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fud is a 2 chain structure with sequence from Oceanobacillus iheyensis HTE831. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: CL, MES, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8EP31_OCEIH Publication Abstract from PubMed Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP bound, allowed us to identify five fixed water molecules that play a significant role in substrate binding. Closure of the beta6-alpha4 loop is revealed as essential not only for pyrophosphate recognition, but also for distal ribose orientation. In addition, a novel structural role for residue D40 is identified. Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O-acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally, mutant G37V supports the participation of a substrate-coordinated water molecule in catalysis that helps to select the proper substrate conformation. Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis.,Zapata-Perez R, Gil-Ortiz F, Martinez-Monino AB, Garcia-Saura AG, Juanhuix J, Sanchez-Ferrer A Open Biol. 2017 Apr;7(4). pii: 160327. doi: 10.1098/rsob.160327. PMID:28446708 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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