5IR4

Crystal structure of wild-type bacterial lipoxygenase from Pseudomonas aeruginosa PA-LOX with space group C2221 at 1.48 A resolution

Summary for 5IR4

• Entry DOI: 10.2210/pdb5ir4/pdb
• Related: 5IR5
• Descriptor: Arachidonate 15-lipoxygenase, FE (II) ION, (2R)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(tetradec-5-enoyloxy)propyl (11Z)-octadec-11-enoate, ... (8 entities in total)
• Functional Keywords: non-heme iron enzyme, protein-phospholipid complex, oxidoreductase, eicosanoids, infectious diseases
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 76607.81

Authors

Kalms, J.,Banthiya, S.,Galemou Yoga, E.,Kuhn, H.,Scheerer, P. (deposition date: 2016-03-12, release date: 2016-08-10, Last modification date: 2024-01-10)

Primary citation

Banthiya, S.,Kalms, J.,Galemou Yoga, E.,Ivanov, I.,Carpena, X.,Hamberg, M.,Kuhn, H.,Scheerer, P.
Structural and functional basis of phospholipid oxygenase activity of bacterial lipoxygenase from Pseudomonas aeruginosa.
Biochim.Biophys.Acta, 1861:1681-1692, 2016

PubMed Abstract: Pseudomonas aeruginosa expresses a secreted LOX-isoform (PA-LOX, LoxA) capable of oxidizing polyenoic fatty acids to hydroperoxy derivatives. Here we report high-level expression of this enzyme in E. coli and its structural and functional characterization. Recombinant PA-LOX oxygenates polyenoic fatty acids including eicosapentaenoic acid and docosahexaenoic acid to the corresponding (n-6)S-hydroperoxy derivatives. This reaction involves abstraction of the proS-hydrogen from the n-8 bisallylic methylene. PA-LOX lacks major leukotriene synthase activity but converts 5S-HETE and 5S,6R/S-DiHETE to anti-inflammatory and pro-resolving lipoxins. It also exhibits phospholipid oxygenase activity as indicated by the formation of a specific pattern of oxygenation products from different phospholipid subspecies. Multiple mutagenesis studies revealed that PA-LOX does not follow classical concepts explaining the reaction specificity of mammalian LOXs. The crystal structure of PA-LOX was solved with resolutions of up to 1.48Å and its polypeptide chain is folded as single domain. The substrate-binding pocket consists of two fatty acid binding subcavities and lobby. Subcavity-1 contains the catalytic non-heme iron. A phosphatidylethanolamine molecule occupies the substrate-binding pocket and its sn1 fatty acid is located close to the catalytic non-heme iron. His377, His382, His555, Asn559 and the C-terminal Ile685 function as direct iron ligands and a water molecule (hydroxyl) completes the octahedral ligand sphere. Although the biological relevance of PA-LOX is still unknown its functional characteristics (lipoxin synthase activity) implicate this enzyme in a bacterial evasion strategy aimed at downregulating the hosts' immune system.

PubMed: 27500637
DOI: 10.1016/j.bbalip.2016.08.002

Experimental method

X-RAY DIFFRACTION (1.48 Å)