Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism 1 1Edited by R. Huber

Putnam, Christopher D.; Arvai, A.S.; Bourne, Yves; Tainer, John A.

doi:10.1006/jmbi.1999.3458

Cited by 419 publications

(391 citation statements)

References 63 publications

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“…In catalases, compound I is formed by heterolysis of hydrogen peroxide and a variety of substrate analogues, ROOH (19). In some catalases, the subsequent transfer of an electron from tyrosine to the porphyrin π-cation radical of compound I gives intermediate II, with an iron oxyferryl and a protein-bound tyrosine radical (20)(21)(22)(23). Since cAOS does not react readily with hydrogen peroxide, and it reacts very rapidly (1400 turnovers s −1 ) with its natural substrate, 8R-hydroperoxyeicosatetraenoic acid (8R-HpETE) (7), it has been of interest to examine whether there are reactions of an intermediate rate, with other hydroperoxides, that might allow cAOS intermediates to be trapped.…”

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confidence: 99%

“…Recently, the site of radical formation in mutant Proteus mirabilis catalase (PMC) was examined by biophysical techniques (23). Although PMC does form a radical when tyrosine is substituted for the native phenylalanine at position 194 (equivalent to Y193 in cAOS), it is argued (21,23) that the BLC radical occurs differently at Y369. Coral AOS has four tyrosines in positions similar to BLC tyrosines: cAOS Y193, Y209, and Y269 and the probable heme ligand, Y353 (equivalent in BLC to Y214, Y230, Y324, and Y357, respectively), but a sequence similar to BLC Y369 and immediate neighbors does not occur in coral AOS (6).…”

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Role of Radical Formation at Tyrosine 193 in the Allene Oxide Synthase Domain of a Lipoxygenase−AOS Fusion Protein from Coral

Katsir

Seavy

et al. 2003

Biochemistry

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Coral allene oxide synthase (cAOS), a fusion protein with 8R-lipoxygenase in Plexaura homomalla, is a hemoprotein with sequence similarity to catalases. cAOS reacts rapidly with the oxidant peracetic acid to form heme compound I and intermediate II. Concomitantly, an electron paramagnetic resonance (EPR) signal with tyrosyl radical-like features, centered at a g-value of 2.004-2.005, is formed. The radical is identified as tyrosyl by changes in EPR spectra when deuterated tyrosine is incorporated in cAOS. The radical location in cAOS is determined by mutagenesis of Y193 and Y209. Upon oxidation, native cAOS and mutant Y209F exhibit the same radical spectrum, but no significant tyrosine radical forms in mutant Y193H, implicating Y193 as the radical site in native cAOS. Estimates of the side chain torsion angles for the radical at Y193, based on the β-proton isotropic EPR hyperfine splitting, A iso , are θ 1 = 21 to 30° and θ 2 = −99 to −90°. The results show that cAOS can cleave nonsubstrate hydroperoxides by a heterolytic path, although a homolytic course is likely taken in converting the normal substrate, 8R-hydroperoxyeicosatetraenoic acid (8R-HpETE), to product. Coral AOS achieves specificity for the allene oxide formed by selection of the homolytic pathway normally, while it inactivates by the heterolytic path with nonoptimal substrates. Accordingly, with the nonoptimal substrate, 13R-hydroperoxyoctadecadienoic acid (13R-HpODE), mutant Y193H is inactivated after turning over significantly fewer substrate molecules than required to inactivate native cAOS or the Y209F mutant because it cannot absorb oxidizing equivalents by forming a radical at Y193. Polyunsaturated fatty acids (PUFAs) 1 are rapidly converted to cell signaling molecules in multistep syntheses involving an initial lipoxygenase or prostaglandin synthase step, followed by further enzymatic conversions (1-3). These multistep syntheses are regulated by localization of the enzymes in subcellular compartments and by protein-protein associations. Examples include synthesis of leukotriene C 4 at the nuclear envelope of leukocytes (4) and synthesis of jasmonic acid by steps which are thought to begin in chloroplasts and to be completed in peroxisomes of green plant cells (5). A fusion protein identified in the coral Plexaura homomalla represents a third mode of regulation, in which an N-terminal catalaselike domain is fused to an 8R-lipoxygenase domain (6). The N-terminal domain (44 kDa) has allene oxide synthase (cAOS) activity with the 8R-hydroperoxide of arachidonic acid (8R- † This research was supported by National Institutes of Health Grant GM36232 (to B.J.G.).* To whom correspondence should be addressed. Phone: (850) 644-8547. Fax: (850) 644-8547. E-mail: gaffney@bio.fsu.edu.. ‡ These authors contributed equally.1 Abbreviations: cAOS, coral allene oxide synthase; BLC, bovine liver catalase; BSA, bovine serum albumin; CYP, cytochrome P450; DES, divinyl ether synthase; EPR, electron paramagnetic resonance; 8R-HpETE, 8R-hydroperoxy-9E,11Z-ei...

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confidence: 99%

mentioning

confidence: 99%

Role of Radical Formation at Tyrosine 193 in the Allene Oxide Synthase Domain of a Lipoxygenase−AOS Fusion Protein from Coral

Katsir

Seavy

et al. 2003

Biochemistry

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“…The novel missense mutations (amino acids 53 and 66) are in the vicinity of these important amino acid residues (28)(29)(30). Therefore, amino acid substitutions in this region (exon 2 T™G at 96 and G™C at 135) may decrease the catalase enzyme activity (60.3 and 58.9 MU/L, respectively vs. the reference range of 113.3"16.5 MU/L).…”

Section: Discussionmentioning

confidence: 99%

Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus

Vitai¹,

Fátrai²,

Rass³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: The enzyme catalase is the main regulator of hydrogen peroxide metabolism. Deficiency of catalase may cause high concentrations of hydrogen peroxide and increase the risk of the development of pathologies for which oxidative stress is a contributing factor, for example, type 2 diabetes mellitus. Catalase deficiency has been reported to be associated with increased frequency of diabetes mellitus in a cohort of patients in Hungary. In this cohort, the majority of mutations in the catalase gene occur in exon 2. Methods: Type 2 diabetic patients (ns308) were evaluated for mutations in intron 1 (81 bp), exon 2 (172 bp) and intron 2 (13 bp) of the catalase gene. Screening for mutations utilized PCR single-strand conformational polymorphism (SSCP) and PCR heteroduplex methods. Verification of detected mutations was by nucleotide sequence analysis. Results: A total of 11 catalase gene mutations were detected in the 308 subjects (3.57%, p-0.001). Five of the 11 were at two previously reported mutation sites: exon 2 (79) G insertion and (138) GA insertion. Six of the 11 were at five previously unreported catalase mutation sites: intron 1 (60) G™T; intron 2 (7) G™A and (5) G™C; exon 2 (96) T™A; and exon 2 (135) T™ A. The novel missense mutations on exon 2 (96 and 135) are associated with 59% and 48% decreased catalase activity, respectively; the novel G™C mutation on intron 2 (5) is associated with a 62% decrease in catalase activity. Mutations detected on intron 1 (60) and intron 2 (7) showed no change in catalase activity. The G™C mutation on intron 2 (5) might be a splicing mutation. The two missense mutations on exon 2 (96) and (135) cause substitutions of amino acids 53 (Asp™Glu) and 66 (Glu™Cys) of the catalase protein.These are close to amino acids that are important for the binding of heme to catalase, 44 (Val) and [72][73][74][75]

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“…This enzyme is commonly used to abolish the formation of tyrosyl radicals [10]. It is known that catalase in the process of decomposing H 2 O 2 forms endogenous tyrosyl radicals [43]. It could be that these radicals are involved in cross-linking TyrFluo tyrosyl radicals to the catalase itself.…”

Section: Discussionmentioning

confidence: 99%

Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore

et al. 2004

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Tyrosyl radicals cross-linked to protein tyrosine residues (tyrosylated proteins) represent hallmarks of neutrophil-mediated injury at the inflammatory locus. Yet the proteins targeted by tyrosyl radicals in an intact cellular system remain to be elucidated. Here, we show that tyrosyl radicals generated by human neutrophils after activation by phorbol 12-myristate 13-acetate (PMA), interferon-g (IFN-g) or TNF-a could act in an autocrine manner by cross-linking to endogenous proteins. We have identified the tyrosylated proteins by using a membraneimpermeable tyrosine analogue, tyramine coupled to fluorescein (TyrFluo), in combination with proteomics techniques. Confocal microscopy images indicated that initially the tyrosylated proteins were localized in patches at the cell surface to become internalized subsequently. In the neutrophil membrane-associated proteome, lactoferrin was the prime target of tyrosylation. Out of three isoforms identified, an 80 kDa neutral isoform was tyrosylated more extensively than the 85 kD basic isoform, particularly after PMA activation. Although all three stimuli induced tyrosylation of the filamentous component vimentin, additional tyrosylated vimentin fragments were detected after IFN-g-and TNF-a-stimulation. Moreover, upon activation the bulk of vimentin behaved as a dimer (M r 120 kDa) being slightly tyrosylated, yet phosphorylated at Thr-425 possibly as a requirement for its externalization. Unexpectedly, bovine catalase added to end tyrosyl radicals formation was detected as a highly tyrosylated neutrophil-associated protein. A moderate stimulus-dependent tyrosylation of ATP synthaseb, a-enolase, glyceraldehyde 3-phosphate dehydrogenase, cytokeratin-10, filamin-A, and annexin-I was also observed. When the membrane-permeable probe (acetylTyrFluo) was used, protein tyrosylation was not observed indicating that the intracellular proteins were well protected against oxidative attack. This study shows that human neutrophils can modulate their proteome via a tyrosine oxidation pathway induced by pro-inflammatory mediators.

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Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism 1 1Edited by R. Huber

Cited by 419 publications

References 63 publications

Role of Radical Formation at Tyrosine 193 in the Allene Oxide Synthase Domain of a Lipoxygenase−AOS Fusion Protein from Coral

Role of Radical Formation at Tyrosine 193 in the Allene Oxide Synthase Domain of a Lipoxygenase−AOS Fusion Protein from Coral

Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus

Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore

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