Function and Mechanism of Zinc Metalloenzymes

McCall, Keith; Huang, Can; Fierke, Carol A.

doi:10.1093/jn/130.5.1437s

Cited by 927 publications

(638 citation statements)

References 108 publications

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“…In fact, zinc supplementation was used to improve the conception rate for up to 80% in RB buffalos (Marai et al, 1992). Zinc is a cofactor for more than 300 metalloenzymes (McCall et al, 2000). These metalloenzymes are spanning all the enzyme classes.…”

Section: Resultsmentioning

confidence: 99%

Blood biochemical profile of Sudanese crossbred repeat breeder cows

Ahmed¹,

Ahmed²,

Frah³

et al. 2017

Afr. J. Biotechnol.

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Repeat breeder (RB) is a cow that fails to conceive from three or more successive insemination, but with normal estrus and absence of detectable clinical abnormalities. It is one of the major problems in dairy production. In the present study, the plasma biochemistry of Sudanese crossbred RB cows was examined. Plasma glucose, total cholesterol (TC), triacylglycerol (TG), total protein (TP) and urea nitrogen were estimated with the spectrophotometer while the plasma levels of Cu, Zn, Fe, and Mn were estimated using the atomic absorption spectroscopy. The results indicate the plasma levels of glucose, Zn, Mn and Fe of RB were significantly lower (P < 0.05) than that of the normal cyclic (NC) cows. Moreover, the plasma level of urea nitrogen of RB was significantly higher (P < 0.05) than that of the NC cows. According to the obtained results, it can be concluded that correcting the plasma glucose, Zn, Mn and Fe as well as lowering the urea nitrogen may be a part of an effective strategy for treatment of repeat breeding syndrome in Sudanese crossbred cows.

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Section: Resultsmentioning

confidence: 99%

Blood biochemical profile of Sudanese crossbred repeat breeder cows

Ahmed¹,

Ahmed²,

Frah³

et al. 2017

Afr. J. Biotechnol.

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“…The nearest -OH group for Zn 2ϩ 3 to associate with is the Glu 122 carboxyl (4.28 Å). Zn 2ϩ has no energetic barrier to multiple coordination geometries and can therefore assume four-or five-membered coordination with relative ease (36). In metalloenzymes, the coordination number of Zn 2ϩ changes to stabilize high-energy intermediates and other transition states (37).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Transmembrane Segment Zinc Binding in the Structure and Function of Rhodopsin

Stojanović

Stitham

Hwa

2004

Journal of Biological Chemistry

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Zinc deficiency and retinitis pigmentosa are both important factors resulting in retinal dysfunction and night blindness. In this study, we address the critical biochemical and structural relevance of zinc ions in rhodopsin and examine whether zinc deficiency can lead to rhodopsin dysfunction. We report the identification of a high-affinity zinc coordination site within the transmembrane domain of rhodopsin, coordinated by the side chains of two highly conserved residues, Glu 122 in transmembrane helix III and His 211 in transmembrane helix V. We also demonstrate that this zinc coordination is critical for rhodopsin folding, 11-cis-retinal binding, and the stability of the chromophore-receptor interaction, defects of which are observed in retinitis pigmentosa. Furthermore, a cluster of retinitis pigmentosa mutations is localized within and around this zinc binding site. Based on these studies, we believe that improvement in zinc binding to rhodopsin at this site within the transmembrane domain may be a pharmacological approach for the treatment of select retinitis pigmentosa mutations. Transmembrane coordination of zinc may also be an important common principle across G-protein-coupled receptors.Several neurodegenerative disorders, Alzheimer disease, Parkinson disease, familial amyotrophic lateral sclerosis, and the transmissible spongiform encephalopathies, share a common pathogenesis involving the misfolding and aggregation of specific proteins. Mounting evidence has demonstrated the direct binding of zinc (Zn 2ϩ ) to the ␤-amyloid (Alzheimer disease), ␣-synuclein (Parkinson disease), superoxide dismutase (amyotrophic lateral sclerosis), and prion (transmissible spongiform encephalopathies) proteins, linking either the gain or loss of Zn 2ϩ binding to the progression of these severe protein misfolding disorders. Zn 2ϩ promotes aggregation of the highly fibrillogenic prion peptide, PrP106 -126 (1), and of the ␤-amyloid protein (2-4) into amyloidogenic aggregates. Clioquinol, a metal chelating agent, is currently being investigated as a potential therapeutic solution to inhibit ␤-amyloid neurotoxicity (5). In contrast, in mutant superoxide dismutase protein, loss of affinity for Zn 2ϩ results in diminished protein activity (6), reduced protein stability (7), and formation of amyloid-like filaments (8). Thus, both zinc deficiencies and excesses can lead to neurodegenerative diseases.In the G protein-coupled photoreceptor rhodopsin, there have been over 100 distinct, heritable mutations identified, many of which induce an altered protein conformation, misfolding, aggregation, and cell death, followed by the clinical manifestation of the retinal neurodegenerative disorder retinitis pigmentosa (9). Interestingly, Zn 2ϩ deficiency is also known to cause retinal neurodegeneration and night blindness (10), symptoms reminiscent of retinitis pigmentosa. Furthermore, Zn 2ϩ has been shown to directly bind rhodopsin (11,12) and to reduce rhodopsin thermal stability and regeneration with 11-cis-retinal at higher Zn 2ϩ concen...

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“…Unlike other first-row transition metals, the zinc atom contains a filled d-orbital and does not participate in redox reactions (22). This lack of redox activity makes Zn 2ϩ an ideal metal cofactor for enzyme catalysis, where it functions as a Lewis acid and accepts a pair of electrons.…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin 2, an Oxidative Stress-induced Protein, Contains a High Affinity Zinc Binding Site

Collet

D'Souza

Jakob

et al. 2003

Journal of Biological Chemistry

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Two thioredoxins have been described in Escherichia coli, TrxA and Trx2. Both thioredoxins are capable of reducing disulfide bonds using a conserved pair of cysteine residues present in a WCGPC motif. A number of unique structural and regulatory features distinguish the Trx2 subfamily from the much larger TrxA family. The Trx2 subfamily has an additional N-terminal domain of ؎ 30 residues, which contains two additional conserved CXXC motifs. Moreover, the gene coding for Trx2 is under control of the oxidative stress transcription factor OxyR in E. coli. This suggests that Trx2 may play a role in the cellular defense against oxidative stress. We show here that Trx2 contains zinc in a 1:1 stoichiometry, making it the first identified zincbinding thioredoxin. The zinc atom is coordinated by the four cysteines of the two N-terminal CXXC motifs. The zinc center of Trx2 binds zinc with a very high affinity (K a of >10 18 M ؊1 ). We show that in vitro oxidation of the zinc binding cysteines by H 2 O 2 releases the zinc and induces a conformational change. The zincfree protein conserves its reductase activity. Altogether, our results suggest that the zinc center might play the role of a redox switch, changing a yet to be identified activity.

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Function and Mechanism of Zinc Metalloenzymes

Cited by 927 publications

References 108 publications

Blood biochemical profile of Sudanese crossbred repeat breeder cows

Blood biochemical profile of Sudanese crossbred repeat breeder cows

Critical Role of Transmembrane Segment Zinc Binding in the Structure and Function of Rhodopsin

Thioredoxin 2, an Oxidative Stress-induced Protein, Contains a High Affinity Zinc Binding Site

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