8V5T

Crystal structure of Alzheimers disease phospholipase D3

Summary for 8V5T

• Entry DOI: 10.2210/pdb8v5t/pdb
• Descriptor: 5'-3' exonuclease PLD3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (5 entities in total)
• Functional Keywords: exonuclease, alzheimer's disease, dna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 112452.66

Authors

Ishii, K.,Hermans, S.J.,Nero, T.L.,Gorman, M.A.,Parker, M.W. (deposition date: 2023-12-01, release date: 2024-10-09, Last modification date: 2025-01-01)

Primary citation

Ishii, K.,Hermans, S.J.,Georgopoulou, M.E.,Nero, T.L.,Hancock, N.C.,Crespi, G.A.N.,Gorman, M.A.,Gooi, J.H.,Parker, M.W.
Crystal structure of Alzheimer's disease phospholipase D3 provides a molecular basis for understanding its normal and pathological functions.
Febs J., 291:5398-5419, 2024

PubMed Abstract: Human 5'-3' exonuclease PLD3, a member of the phospholipase D family of enzymes, has been validated as a therapeutic target for treating Alzheimer's disease. Here, we have determined the crystal structure of the luminal domain of the enzyme at 2.3 Å resolution, revealing a bilobal structure with a catalytic site located between the lobes. We then compared the structure with published crystal structures of other human PLD family members which revealed that a number of catalytic and lipid recognition residues, previously shown to be key for phospholipase activity, are not conserved or, are absent. This led us to test whether the enzyme is actually a phospholipase. We could not measure any phospholipase activity but the enzyme shows robust nuclease activity. Finally, we have mapped key single nucleotide polymorphisms onto the structure which reveals plausible reasons as to why they have an impact on Alzheimer's disease.

PubMed: 39325669
DOI: 10.1111/febs.17277

Experimental method

X-RAY DIFFRACTION (2.3 Å)