Structure of a dehydratase–isomerase from the bacterial pathway for biosynthesis of unsaturated fatty acids: two catalytic activities in one active site

Leesong, Minsun; Henderson, Barry; Gillig, James R.; Schwab, John M.; Smith, Janet L.

doi:10.1016/s0969-2126(96)00030-5

Cited by 260 publications

(368 citation statements)

References 43 publications

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“…The crystal of -hydroxydecanoyl thiol ester dehydrase (Leesong et al, 1996) with 2 Â 171 amino acids in an asymmetric unit, unit cell of P2 1 2 1 2 1 symmetry (a = 59.7, b = 66.9, c = 86.0 A Ê ), was measured at Cu K wavelength with an R-axisII detector. An anomalous signal comes from 2 Â 9 single sulfur atoms.…”

Section: Global and Local Scalingmentioning

confidence: 99%

Multiparametric scaling of diffraction intensities

Otwinowski

Borek

Majewski

et al. 2003

Acta Crystallogr A Found Crystallogr

657

499

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A novel and general approach to scaling diffraction intensities is presented. The method minimizes the disagreement among multiple measurements of symmetry-related re¯ections using a stable re®nement procedure. The scale factors are described by a¯exible exponential function that allows different scaling corrections to be chosen and combined according to the needs of the experiment. The scaling model presented here includes: scale and temperature factor per batch of data; temperature factor as a continuous function of the radiation dose; absorption in the crystal; uneven exposure within a single diffraction image; and corrections for phenomena that depend on the diffraction peak position on the detector. This scaling model can be extended to include additional corrections for various instrumental and data-collection problems.

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Section: Global and Local Scalingmentioning

confidence: 99%

Multiparametric scaling of diffraction intensities

Otwinowski

Borek

Majewski

et al. 2003

Acta Crystallogr A Found Crystallogr

657

499

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“…long-chain acyl-CoA substrates with fatty acid chains of [8][9][10][11][12][13][14][15][16] carbon atoms (C 8 -C 16 ) (7,13). Acot7 contains a pair of fused thioesterase domains that share Ϸ30% sequence identity, with each thioesterase domain predicted to have the hotdog fold structure with an ␣-helix sausage wrapped by a ␤-sheet bun (14)(15)(16).…”

mentioning

confidence: 99%

“…Acot7 contains a pair of fused thioesterase domains that share Ϸ30% sequence identity, with each thioesterase domain predicted to have the hotdog fold structure with an ␣-helix sausage wrapped by a ␤-sheet bun (14)(15)(16).…”

mentioning

confidence: 99%

Structural basis for recruitment of tandem hotdog domains in acyl-CoA thioesterase 7 and its role in inflammation

Forwood¹,

Thakur²,

Gunčar

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Acyl-CoA thioesterases (Acots) catalyze the hydrolysis of fatty acyl-CoA to free fatty acid and CoA and thereby regulate lipid metabolism and cellular signaling. We present a comprehensive structural and functional characterization of mouse acyl-CoA thioesterase 7 (Acot7). Whereas prokaryotic homologues possess a single thioesterase domain, mammalian Acot7 contains a pair of domains in tandem. We determined the crystal structures of both the N-and C-terminal domains of the mouse enzyme, and inferred the structure of the full-length enzyme using a combination of chemical cross-linking, mass spectrometry, and molecular modeling. The quaternary arrangement in Acot7 features a trimer of hotdog fold dimers. Both domains of Acot7 are required for activity, but only one of two possible active sites in the dimer is functional. Asn-24 and Asp-213 (from N-and C-domains, respectively) were identified as the catalytic residues through sitedirected mutagenesis. An enzyme with higher activity than wildtype Acot7 was obtained by mutating the residues in the nonfunctional active site. Recombinant Acot7 was shown to have the highest activity toward arachidonoyl-CoA, suggesting a function in eicosanoid metabolism. In line with the proposal, Acot7 was shown to be highly expressed in macrophages and up-regulated by lipopolysaccharide. Overexpression of Acot7 in a macrophage cell line modified the production of prostaglandins D2 and E2. Together, the results link the molecular and cellular functions of Acot7 and identify the enzyme as a candidate drug target in inflammatory disease.domain duplication ͉ macrophage ͉ protein structure ͉ acyl-coenzyme A hydrolase ͉ lipid metabolism

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“…The final structure of the XC229 monomer adopts a hotdog motif 5 comprising a fivestranded, antiparallel ␤-sheet labeled ␤1-␤5, with a 25431 topology as shown in Figure 1(b). In addition to the major ␤-sheet, a second, short, two-stranded antiparallel ␤-sheet is also observed at the bottom left corner of the protein, referring to the figure orientation.…”

mentioning

confidence: 99%