2FNQ

Insights from the X-ray crystal structure of coral 8R-lipoxygenase: calcium activation via A C2-like domain and a structural basis of product chirality

Replaces:  1ZQ4

Summary for 2FNQ

• Entry DOI: 10.2210/pdb2fnq/pdb
• Related: 1u5u
• Descriptor: Allene oxide synthase-lipoxygenase protein, FE (II) ION, CALCIUM ION (3 entities in total)
• Functional Keywords: beta-barrel, eicosanoid, fatty acid, c2-like domain, oxidoreductase
• Biological source: Plexaura homomalla
• Cellular location: Cytoplasm: O16025
• Total number of polymer chains: 2
• Total formula weight: 160227.22

Authors

Oldham, M.L.,Brash, A.R.,Newcomer, M.E. (deposition date: 2006-01-11, release date: 2006-02-28, Last modification date: 2024-02-14)

Primary citation

Oldham, M.L.,Brash, A.R.,Newcomer, M.E.
Insights from the X-ray crystal structure of coral 8R-lipoxygenase: calcium activation via a C2-like domain and a structural basis of product chirality.
J.Biol.Chem., 280:39545-39552, 2005

PubMed Abstract: Lipoxygenases (LOXs) catalyze the regio- and stereospecific dioxygenation of polyunsaturated membrane-embedded fatty acids. We report here the 3.2 A resolution structure of 8R-LOX from the Caribbean sea whip coral Plexaura homomalla, a LOX isozyme with calcium dependence and the uncommon R chiral stereospecificity. Structural and spectroscopic analyses demonstrated calcium binding in a C2-like membrane-binding domain, illuminating the function of similar amino acids in calcium-activated mammalian 5-LOX, the key enzyme in the pathway to the pro-inflammatory leukotrienes. Mutation of Ca(2+)-ligating amino acids in 8R-LOX resulted not only in a diminished capacity to bind membranes, as monitored by fluorescence resonance energy transfer, but also in an associated loss of Ca(2+)-regulated enzyme activity. Moreover, a structural basis for R chiral specificity is also revealed; creation of a small oxygen pocket next to Gly(428) (Ala in all S-LOX isozymes) promoted C-8 oxygenation with R chirality on the activated fatty acid substrate.

PubMed: 16162493
DOI: 10.1074/jbc.M506675200

Experimental method

X-RAY DIFFRACTION (3.2 Å)