5tup

X-ray Crystal Structure of the Aspergillus fumigatus Sliding Clamp

spinqualitylabelsall models 5tup, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tup is a 3 chain structure with sequence from Aspergillus fumigatus Z5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.602Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0J5SJF1_ASPFM This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand.[RuleBase:RU000641] Publication Abstract from PubMed The fungal pathogen Aspergillus fumigatus has been implicated in a drastic increase in life-threatening infections over the past decade. However, compared to other microbial pathogens, little is known about the essential molecular processes of this organism. One such fundamental process is DNA replication. The protein responsible for ensuring processive DNA replication is PCNA (proliferating cell nuclear antigen, also known as the sliding clamp), which clamps the replicative polymerase to DNA. Here we present the first crystal structure of a sliding clamp from a pathogenic fungus (A. fumigatus), at 2.6A. Surprisingly, the structure bears more similarity to the human sliding clamp than other available fungal sliding clamps. Reflecting this, fluorescence polarization experiments demonstrated that AfumPCNA interacts with the PCNA-interacting protein (PIP-box) motif of human p21 with an affinity (Kd ) of 3.1 mum. Molecular dynamics simulations were carried out to better understand how AfumPCNA interacts with human p21. These simulations revealed that the PIP-box bound to AfuPCNA forms a secondary structure similar to that observed in the human complex, with a central 310 helix contacting the hydrophobic surface pocket of AfumPCNA as well as a beta-strand that forms an antiparallel sheet with the AfumPCNA surface. Differences in the 310 helix interaction with PCNA, attributed to residue Thr131 of AfumPCNA, and a less stable beta-strand formation, attributed to residues Gln123 and His125 of AfumPCNA, are likely causes of the over 10-fold lower affinity of the p21 PIP-box for AfumPCNA as compared to hPCNA. DATABASE: The atomic coordinates and structure factors for the Aspergillus fumigatus sliding clamp can be found in the RCSB Protein Data Bank (https://www.rcsb.org) under the accession code 5TUP. Structure of the sliding clamp from the fungal pathogen Aspergillus fumigatus (AfumPCNA) and interactions with Human p21.,Marshall AC, Kroker AJ, Murray LA, Gronthos K, Rajapaksha H, Wegener KL, Bruning JB FEBS J. 2017 Feb 6. doi: 10.1111/febs.14035. PMID:28165677 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proliferating cell nuclear antigen 3D structures

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