Structure of manganese(II) glycolate dihydrate

Lis, Tadeusz

doi:10.1107/s0567740880004190

Cited by 22 publications

(17 citation statements)

References 10 publications

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“…2). The mode of glycolate binding observed in the protein crystal is distinct from that observed in small molecule inorganic complexes of Mn(II) and glycolate (27). In the latter case, the hydroxy acid exhibits bidentate coordination via both carboxylate and hydroxyl functions, requiring anti-stereochemistry for the carboxylate-metal interactions.…”

Section: Resultsmentioning

confidence: 76%

Structural and Spectroscopic Studies Shed Light on the Mechanism of Oxalate Oxidase

Opaleye

Rose

Whittaker

et al. 2006

Journal of Biological Chemistry

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Oxalate oxidase (EC 1.2.3.4) catalyzes the conversion of oxalate and dioxygen to hydrogen peroxide and carbon dioxide. In this study, glycolate was used as a structural analogue of oxalate to investigate substrate binding in the crystalline enzyme. The observed monodentate binding of glycolate to the active site manganese ion of oxalate oxidase is consistent with a mechanism involving C-C bond cleavage driven by superoxide anion attack on a monodentate coordinated substrate. In this mechanism, the metal serves two functions: to organize the substrates (oxalate and dioxygen) and to transiently reduce dioxygen. The observed structure further implies important roles for specific active site residues (two asparagines and one glutamine) in correctly orientating the substrates and reaction intermediates for catalysis. Combined spectroscopic, biochemical, and structural analyses of mutants confirms the importance of the asparagine residues in organizing a functional active site complex.Oxalate oxidase (OXO; EC 1.2.3.4) 6 catalyzes the oxidation of oxalate, reducing dioxygen to hydrogen peroxide and forming 2 mol of carbonOxalate oxidase is widespread in nature and has been found in bacteria (4), fungi (1, 5), and various plant tissues (6). It has been detected in barley seedling roots during germination and in the leaves of mature barley plants in response to powdery mildew infection (6, 7), suggesting a role in plant signaling and defense. The enzyme has been purified to homogeneity from barley seedling roots and its N-terminal sequence determined, allowing the corresponding cDNA to be isolated and the complete primary sequence to be determined (3,8). These developments led to the recognition that the enzyme, OXO, is identical to an important marker of grain development during germination of wheat called germin (3,8). OXO is a member of a functionally diverse protein superfamily known as the cupins (9) or double stranded ␤-helix proteins (10). Barley OXO forms a hexamer that has extreme stability to heat and proteolysis (11).Spectroscopic studies demonstrated that OXO requires manganese for catalysis (12) and subsequent crystallographic studies on the barley enzyme revealed the structure of the hexamer (Fig. 1a) and confirmed the presence of a mononuclear manganese center buried deep within its jellyroll ␤-barrel domain (13). The manganese is bound by the side chains of three histidines and one glutamate residue, as well as two water molecules that occupy adjacent positions in the roughly octahedral metal complex (Fig. 1b). Based on the lack of obvious optical absorption and the presence of a characteristic EPR spectrum, the manganese ion has been assigned as the reduced Mn(II) oxidation state in the resting enzyme (12). Spectroscopic studies using recombinant OXO expressed in Pichia pastoris confirmed the presence of Mn(II) in the resting recombinant enzyme and provided the first spectroscopic evidence for oxalate binding to the manganese (14). The EPR signal of the anaerobic substrate complex, like that of the nativ...

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Section: Resultsmentioning

confidence: 76%

Structural and Spectroscopic Studies Shed Light on the Mechanism of Oxalate Oxidase

Opaleye

Rose

Whittaker

et al. 2006

Journal of Biological Chemistry

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“…In the small molecule model studies, glycolate exhibits bidentate coordination. 68 The protein complex may exhibit the extended, monodentate coordination due to steric barriers disfavoring bidentate coordination, with specific stabilization of monodentate ligation through steric interactions with active site residues. A similar mode of substrate binding, where oxalate binds in an end-on conformation providing an empty coordination site for dioxygen ligand was observed in oxalate decarboxylase.…”

Section: Enzymes Structurally and Functionally Similar To Ardmentioning

confidence: 99%

The Metal Drives the Chemistry: Dual Functions of Acireductone Dioxygenase

2017

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Acireductone dioxygenase (ARD) from the methionine salvage pathway (MSP) is a unique enzyme that exhibits dual chemistry determined solely by the identity of the divalent transition metal ion (Fe2+ or Ni2+) in the active site. The Fe2+ containing isozyme catalyzes the on-pathway reaction using substrates 1,2 dihydroxy-3-keto-5-methylthiopent-1-ene (acireductone) and dioxygen to generate formate and the ketoacid precursor of methionine, 2-keto-4-methylthiobutyrate, whereas the Ni2+ containing isozyme catalyzes an off-pathway shunt with the same substrates, generating methylthiopropionate, carbon monoxide and formate. The dual chemistry of ARD was originally discovered in the bacterium Klebsiella oxytoca, but it has recently been shown that mammalian ARD enzymes (mouse and human) are also capable of catalyzing metal-dependent dual chemistry in vitro. This is particularly interesting since carbon monoxide, one of the products of off-pathway reaction, has been identified as an anti-apoptotic molecule in mammals. In addition, several biochemical and genetic studies have indicated an inhibitory role of human ARD in cancer. This comprehensive review describes the biochemical and structural characterization of the ARD family, the proposed experimental and theoretical approaches to establishing mechanisms for the dual chemistry, insights into the mechanism based on comparison with structurally and functionally similar enzymes and the applications of this research to the field of artificial metalloenzymes and synthetic biology.

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“…Examples include the oxo-centred trinuclear complexes [1] as well as [Mn 12 O 12 (O 2 CCH 3 ) 16 (OH 2 ) 4 ]·4(H 2 O)·2(CH 3 CO 2 H) [2] and its related clusters synthesized with other carboxylic acids [3] which show the behaviour characteristic of ''single molecule magnets''. In addition to the interest in polynuclear clusters, much research on framework structures produced hydrothermally with carboxylates and related donors has been performed.…”

Section: Introductionmentioning

confidence: 99%

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2 , and the structure of this phase has been determined by Xray diffraction. The same product can be obtained by solidstate dehydration of single crystals of manganese formate dihydrate, giving crystals that, although of poor quality, still allow for a single crystal structure determination.

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mentioning

confidence: 99%