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PDBsum entry 4pkb
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Hydrolase/hydrolase inhibitor
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PDB id
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4pkb
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References listed in PDB file
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Key reference
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Title
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Crystal structure of patatin-17 in complex with aged and non-Aged organophosphorus compounds.
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Authors
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S.J.Wijeyesakere,
R.J.Richardson,
J.A.Stuckey.
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Ref.
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Plos One, 2014,
9,
e108245.
[DOI no: ]
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PubMed id
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Abstract
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Patatin is a non-specific plant lipase and the eponymous member of a broad class
of serine hydrolases termed the patatin-like phospholipase domain containing
proteins (PNPLAs). Certain PNPLA family members can be inhibited by
organophosphorus (OP) compounds. Currently, no structural data are available on
the modes of interaction between the PNPLAs and OP compounds or their native
substrates. To this end, we present the crystal structure of patatin-17 (pat17)
in its native state as well as following inhibition with methyl arachidonyl
fluorophosphonate (MAFP) and inhibition/aging with
diisopropylphosphorofluoridate (DFP). The native pat17 structure revealed the
existence of two portals (portal1 and portal2) that lead to its active-site
chamber. The DFP-inhibited enzyme underwent the aging process with the
negatively charged phosphoryl oxygen, resulting from the loss of an isopropyl
group, being within hydrogen-binding distance to the oxyanion hole. The
MAFP-inhibited pat17 structure showed that MAFP did not age following its
interaction with the nucleophilic serine residue (Ser77) of pat17 since its
O-methyl group was intact. The MAFP moiety is oriented with its phosphoryl
oxygen in close proximity to the oxyanion hole of pat17 and its O-methyl group
located farther away from the oxyanion hole of pat17 relative to the DFP-bound
state. The orientation of the alkoxy oxygens within the two OP compounds
suggests a role for the oxyanion hole in stabilizing the emerging negative
charge on the oxygen during the aging reaction. The arachidonic acid side chain
of MAFP could be contained within portals 1 or 2. Comparisons of pat17 in the
native, inhibited, and aged states showed no significant global conformational
changes with respect to their Cα backbones, consistent with observations from
other α/β hydrolases such as group VIIA phospholipase A2.
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