NADH peroxidase

Last updated
NADH peroxidase
Structure of NADH Peroxidase from Enterococcus faecalis.png
The structure of NADH peroxidase from Enterococcus faecalis. Adapted from PDB: 2NPX ​.
Identifiers
EC no. 1.11.1.1
CAS no. 9032-24-0
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins

In enzymology, a NADH peroxidase (EC 1.11.1.1) is an enzyme that catalyzes the chemical reaction

Contents

NADH + H+ + H2O2 NAD+ + 2 H2O

The presumed function of NADH peroxidase is to inactivate H2O2 generated within the cell, for example by glycerol-3-phosphate oxidase during glycerol metabolism or dismutation of superoxide, before the H2O2 causes damage to essential cellular components. [1]

The 3 substrates of this enzyme are NADH, H+, and H2O2, whereas its two products are NAD+ and H2O. It employs one cofactor, FAD, however no discrete FADH2 intermediate has been observed. [2]

This enzyme belongs to the family of oxidoreductases, specifically those acting on a peroxide as acceptor (peroxidases). The systematic name of this enzyme class is NADH:hydrogen-peroxide oxidoreductase. Other names in common use include DPNH peroxidase, NAD peroxidase, diphosphopyridine nucleotide peroxidase, NADH-peroxidase, nicotinamide adenine dinucleotide peroxidase, and NADH2 peroxidase.

Structure

The crystal structure of NADH peroxidase resembles glutathione reductase with respect to chain fold and location as well as conformation of the prosthetic group FAD [3]

His10 of the NADH peroxidase is located near the N-terminus of the R1 helix within the FAD-binding site. [4] One of the oxygen atoms of Cys42-SO3H is hydrogen-bonded both to the His10 imidazole and to Cys42 N terminus. The His10 functions in part to stabilize the unusual Cys42-SOH redox center. [3] Arg303 also stabilizes the Cys42-SO3H. Glu-14 participates in forming the tight dimer interface that limits solvent accessibility, important for maintaining the oxidation state of the sulfenic acid. [4]

Alignment of NADH, FAD and Cysteine 42 in NADH Peroxidase, Adapted from PDB 2NPX Alignment of NADH, FAD and Cysteine 42 in NADH Peroxidase.png
Alignment of NADH, FAD and Cysteine 42 in NADH Peroxidase, Adapted from PDB 2NPX
Four residues essential for active site functionality in NADH Peroxidase, Adapted from PDB 2NPX Four residues essential for active site functionality in NADH Peroxidase.png
Four residues essential for active site functionality in NADH Peroxidase, Adapted from PDB 2NPX

Reaction mechanism

The NADH peroxidase from Enterococcus faecalis is unique in that it utilizes the Cys42 thiol/sulfenic acid (-SH/-SOH) redox couple in the heterolytic cleavage of the peroxide bond to catalyze the two-electron reduction of hydrogen peroxide to water. [5]

The kinetic mechanism of the wild-type peroxidase involves (1) NADH reduction of E(FAD, Cys42-SOH) to EH2(FAD, Cys42-SH) in an initial priming step; (2) rapid binding of NADH to EH2; (3) reduction of H2O2 by the Cys42-thiolate, yielding E•NADH; and (4) rate-limiting hydride transfer from bound NADH, regenerating EH2. [6] No discrete FADH2 intermediate has been observed, however, and the precise details of Cys42-SOH reduction have not been elucidated. [7]

  1. E + NADH → (EH2'•NAD+)* → EH2'•NAD+→ EH2 + NAD+ + H2O
  2. EH2 + NADH → EH2•NADH*
  3. EH2•NADH* + H2O2→ E•NADH + H2O
  4. E•NADH + H+→ EH2•NAD+ + H2O
  5. EH2•NAD+→ EH2 + NAD+

Inhibitors include Ag+, Cl−, Co2+, Cu2+, Hg2+, NaN3, Pb2+, and SO42−. [8] At suboptimal H2O2 concentrations and concentrations of NADH that are saturating, NADH inhibits the peroxidase activity of the NADH peroxidase by converting the enzyme to an unstable intermediate. NAD+ behaves as an activator by reversing the equilibria that lead to the unstable intermediate, thus converting the enzyme to the kinetically active complex that reduces H2O2. [9]

Biological Function

NADH eliminates potentially toxic hydrogen peroxide under aerobic growth conditions and represents an enzymatic defense available against H2O2-mediated oxidative stress. Second, the enzyme presents an additional mechanism for regeneration of the NAD+ essential to the strictly fermentative metabolism of this organism. [2] [10] The enzyme may also protect against exogenous H2O2 and contribute to bacterial virulence. [11]

The actual function of NADH peroxidases and oxidases in plants is still unclear, but they could act in early signaling of oxidative stress through producing H2O2. [12]

An alternative role may include regulation of H2O2 formation by NADH peroxidase and oxidase in cell wall loosening and reconstruction. [13]

Related Research Articles

<span class="mw-page-title-main">Hydrogen peroxide</span> Chemical compound

Hydrogen peroxide is a chemical compound with the formula H2O2. In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution in water for consumer use and in higher concentrations for industrial use. Concentrated hydrogen peroxide, or "high-test peroxide", decomposes explosively when heated and has been used as both a monopropellant and an oxidizer in rocketry.

<span class="mw-page-title-main">Catalase</span> Enzyme decomposing hydrogen peroxide

Catalase is a common enzyme found in nearly all living organisms exposed to oxygen which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS). Catalase has one of the highest turnover numbers of all enzymes; one catalase molecule can convert millions of hydrogen peroxide molecules to water and oxygen each second.

A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.

<span class="mw-page-title-main">Glucose oxidase</span> Class of enzymes

The glucose oxidase enzyme also known as notatin is an oxidoreductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. This enzyme is produced by certain species of fungi and insects and displays antibacterial activity when oxygen and glucose are present.

<span class="mw-page-title-main">Nicotinamide adenine dinucleotide phosphate</span> Chemical compound

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP+ is the oxidized form. NADP+ is used by all forms of cellular life.

Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.

Any enzyme system that includes cytochrome P450 protein or domain can be called a P450-containing system.

<span class="mw-page-title-main">Ascorbate peroxidase</span> Enzyme

Ascorbate peroxidase (or L-ascorbate peroxidase, APX or APEX) (EC 1.11.1.11) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">4-Hydroxyphenylacetate 3-monooxygenase</span> Class of enzymes

4-hydroxyphenylacetate 3-monooxygenase (EC 1.14.14.9) is an enzyme that catalyzes the chemical reaction

In enzymology, a malate oxidase (EC 1.1.3.3) is an enzyme that catalyzes the chemical reaction

In enzymology, a fatty-acid peroxidase (EC 1.11.1.3) is an enzyme that catalyzes the chemical reaction

In enzymology, a lignin peroxidase (EC 1.11.1.14) is an enzyme that catalyzes the chemical reaction

In enzymology, a manganese peroxidase (EC 1.11.1.13) is an enzyme that catalyzes the chemical reaction

In enzymology, a NADPH peroxidase (EC 1.11.1.2) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Renalase</span> Mammalian protein found in Homo sapiens

Renalase, FAD-dependent amine oxidase is an enzyme that in humans is encoded by the RNLS gene. Renalase is a flavin adenine dinucleotide-dependent amine oxidase that is secreted into the blood from the kidney.

Hypothiocyanite is the anion [OSCN]− and the conjugate base of hypothiocyanous acid (HOSCN). It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group. Hypothiocyanous acid is a fairly weak acid; its acid dissociation constant (pKa) is 5.3.

<span class="mw-page-title-main">Lactoperoxidase</span> Mammalian protein found in Homo sapiens

Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary and other mucosal glands including the lungs, bronchii and nose that functions as a natural and the first line of defense against bacteria and viruses. Lactoperoxidase is a member of the heme peroxidase family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene.

Haem peroxidases (or heme peroxidases) are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. Most haem peroxidases follow the reaction scheme:

<span class="mw-page-title-main">Selenenic acid</span> Class of chemical compounds

A selenenic acid is an organoselenium compound and an oxoacid with the general formula RSeOH, where R ≠ H. It is the first member of the family of organoselenium oxoacids, which also include seleninic acids and selenonic acids, which are RSeO2H and RSeO3H, respectively. Selenenic acids derived from selenoenzymes are thought to be responsible for the antioxidant activity of these enzymes. This functional group is sometimes called SeO-selenoperoxol.

<span class="mw-page-title-main">NADH:ubiquinone reductase (non-electrogenic)</span> Class of enzymes

NADH:ubiquinone reductase (non-electrogenic) (EC 1.6.5.9, NDH-2, ubiquinone reductase, coenzyme Q reductase, dihydronicotinamide adenine dinucleotide-coenzyme Q reductase, DPNH-coenzyme Q reductase, DPNH-ubiquinone reductase, NADH-coenzyme Q oxidoreductase, NADH-coenzyme Q reductase, NADH-CoQ oxidoreductase, NADH-CoQ reductase) is an enzyme with systematic name NADH:ubiquinone oxidoreductase. This enzyme catalyses the following chemical reaction:

References

  1. ↑ La Carbona S, Sauvageot N, Giard JC, Benachour A, Posteraro B, Auffray Y, Sanguinetti M, Hartke A (December 2007). "Comparative study of the physiological roles of three peroxidases (NADH peroxidase, Alkyl hydroperoxide reductase and Thiol peroxidase) in oxidative stress response, survival inside macrophages and virulence of Enterococcus faecalis". Mol. Microbiol. 66 (5): 1148–63. doi: 10.1111/j.1365-2958.2007.05987.x . PMID   17971082. S2CID   40046805.
  2. 1 2 Miller H, Poole LB, Claiborne A (June 1990). "Heterogeneity among the flavin-containing NADH peroxidases of group D streptococci. Analysis of the enzyme from Streptococcus faecalis ATCC 9790". J. Biol. Chem. 265 (17): 9857–63. doi: 10.1016/S0021-9258(19)38750-2 . PMID   2161844.
  3. 1 2 Stehle T, Claiborne A, Schulz GE (January 1993). "NADH binding site and catalysis of NADH peroxidase". Eur. J. Biochem. 211 (1–2): 221–6. doi: 10.1111/j.1432-1033.1993.tb19889.x . PMID   8425532.
  4. 1 2 Yeh JI, Claiborne A (2002). "Crystal Structures of Oxidized and Reduced Forms of NADH Peroxidase". Redox Cell Biology and Genetics Part B. Methods in Enzymology. Vol. 353. pp.  44–54. doi:10.1016/S0076-6879(02)53035-4. ISBN   978-0-12-182256-9. PMID   12078517.
  5. ↑ Crane EJ, Yeh JI, Luba J, Claiborne A (August 2000). "Analysis of the kinetic and redox properties of the NADH peroxidase R303M mutant: correlation with the crystal structure". Biochemistry. 39 (34): 10353–64. doi:10.1021/bi000553m. PMID   10956025.
  6. ↑ Crane EJ, Parsonage D, Poole LB, Claiborne A (October 1995). "Analysis of the kinetic mechanism of enterococcal NADH peroxidase reveals catalytic roles for NADH complexes with both oxidized and two-electron-reduced enzyme forms". Biochemistry. 34 (43): 14114–24. doi:10.1021/bi00043a016. PMID   7578008.
  7. ↑ Crane EJ, Parsonage D, Claiborne A (February 1996). "The active-site histidine-10 of enterococcal NADH peroxidase is not essential for catalytic activity". Biochemistry. 35 (7): 2380–7. doi:10.1021/bi952347y. PMID   8652580.
  8. ↑ Dolin MI (March 1957). "The Streptococcus faecalis oxidases for reduced diphosphopyridine nucleotide. III. Isolation and properties of a flavin peroxidase for reduced diphosphopyridine nucleotide". J. Biol. Chem. 225 (1): 557–73. doi: 10.1016/S0021-9258(18)64952-X . PMID   13416259.
  9. ↑ Dolin MI (September 1977). "DPNH peroxidase: effector activities of DPN" (PDF). Biochem. Biophys. Res. Commun. 78 (1): 393–400. doi:10.1016/0006-291X(77)91267-0. hdl: 2027.42/22844 . PMID   199166.
  10. ↑ Hansson L, Häggström MH (1984). "Effects of growth conditions on the activities of superoxide dismutase and NADH-oxidase/NADH-peroxidase inStreptococcus lactis". Current Microbiology. 10 (6): 345–351. doi:10.1007/BF01626563. S2CID   27660179.
  11. ↑ Gordon J, Holman RA, McLeod JW (October 1953). "Further observations on the production of hydrogen peroxide by anaerobic bacteria". J Pathol Bacteriol. 66 (2): 527–37. doi:10.1002/path.1700660224. PMID   13118459.
  12. ↑ Šimonovičová M, Tamás L, Huttová J, Mistrík I (2004). "Effect of Aluminium on Oxidative Stress Related Enzymes Activities in Barley Roots". Biologia Plantarum. 48 (2): 261–266. doi: 10.1023/B:BIOP.0000033454.95515.8a . S2CID   34802416.
  13. ↑ Chen SX, Schopfer P (March 1999). "Hydroxyl-radical production in physiological reactions. A novel function of peroxidase". Eur. J. Biochem. 260 (3): 726–35. doi:10.1046/j.1432-1327.1999.00199.x. PMID   10103001.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.