Monooxygenase

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (10:11, 5 January 2025) (edit) (undo)
 
(12 intermediate revisions not shown.)
Line 1: Line 1:
-
<StructureSection load='5tkh' size='350' side='right' scene='' caption='Lytic polysaccharide monooxygenase complex with Cu(II) and PEG (PDB code [[5tkh]])' >
+
<StructureSection load='5tkh' size='350' side='right' scene='' caption='Glycosylated lytic polysaccharide monooxygenase complex with Cu(II) (orange) and peroxide (PDB code [[5tkh]])' >
-
 
+
__TOC__
== Function ==
== Function ==
'''Monooxygenases''' (MO) catalyzes the incorporation of a hydroxyl group into a variety of substrates. MO catalyzes the reduction of O<sub>2</sub> to H<sub>2</sub>O while oxidating NADPH.
'''Monooxygenases''' (MO) catalyzes the incorporation of a hydroxyl group into a variety of substrates. MO catalyzes the reduction of O<sub>2</sub> to H<sub>2</sub>O while oxidating NADPH.
 +
*'''ActVA-Orf6 monooxygenase''' catalyses the oxidation of an aromatic intermediate of the actinorhodin pathway <ref>PMID:12514126</ref>.
 +
*'''Baeyer-Villigen monooxygenase''' is a bioanalytic tool which can catalyze reactions which are difficult to do via chemical means<ref>PMID:15599520</ref>.
 +
*'''TropB monooxygenase''' catalyses asymmetric oxidative dearomatization reactions <ref>PMID:31346489</ref>.
 +
*'''TetX monooxygenase''' inactivates the tetracycline antibiotic <ref>PMID:15452119</ref>.
 +
*'''Phenol 2-monooxygenase''' see [[Phenol hydroxylase (hebrew)]].
=== Peptidylglycine α-Hydroxylating Monooxygenase (PHM)-coordination of peroxide to Cu<sub>M</sub> center. Structural and computational study <ref >doi 10.1007/s00775-012-0967-z</ref>===
=== Peptidylglycine α-Hydroxylating Monooxygenase (PHM)-coordination of peroxide to Cu<sub>M</sub> center. Structural and computational study <ref >doi 10.1007/s00775-012-0967-z</ref>===
Line 9: Line 14:
In recent years there has been a significant interest in describing the interactions of copper-containing enzymes with O<sub>2</sub>/H<sub>2</sub>O<sub>2</sub>-derived species. The short-lived intermediates resulting from the activation of dioxygen are the key players in the mechanistic cycles in many metalloenzymes. In the enzyme <scene name='Journal:JBIC:17/Cv/3'>peptidylglycine alpha-hydroxylating monooxygenase (PHM)</scene> various reduced Cu/oxygen species have been proposed to act as catalytically competent intermediates, yet their exact nature and their role in the enzymatic reaction is still unknown.
In recent years there has been a significant interest in describing the interactions of copper-containing enzymes with O<sub>2</sub>/H<sub>2</sub>O<sub>2</sub>-derived species. The short-lived intermediates resulting from the activation of dioxygen are the key players in the mechanistic cycles in many metalloenzymes. In the enzyme <scene name='Journal:JBIC:17/Cv/3'>peptidylglycine alpha-hydroxylating monooxygenase (PHM)</scene> various reduced Cu/oxygen species have been proposed to act as catalytically competent intermediates, yet their exact nature and their role in the enzymatic reaction is still unknown.
Structural and other studies showed that peptidylglycine &#945;-hydroxylating monooxygenase (PHM) contains <scene name='Journal:JBIC:17/Cv/4'>two non-equivalent copper sites (CuH and CuM)</scene>. CuM serves as an oxygen binding and hydrogen abstraction site, CuH is involved in electron transfer. In the structure of Cu(II)-PHM complexed with hydrogen peroxide determined to 1.98 Å resolution, <scene name='Journal:JBIC:17/Cv/7'>(hydro)peroxide binds exclusively to CuM in a slightly asymmetric side-on mode</scene>. The <scene name='Journal:JBIC:17/Cv/8'>interatomic O-O distance of the copper-bound ligand is 1.5, characteristic of peroxide/hydroperoxide species, and the copper-oxygen distances are 2.0 and 2.1</scene> Å. This Cu(II)-bound <scene name='Journal:JBIC:17/Cv/9'>peroxo moiety interacts closely with a molecule of water</scene>, forming <scene name='Journal:JBIC:17/Cv/10'>hydrogen bonds that stabilize the structure</scene>. DFT and QM/MM calculations indicate that this species is a Cu-bound doubly deprotonated peroxidate and that its energy is similar to that of its isomer Cu(I)-bound superoxide.
Structural and other studies showed that peptidylglycine &#945;-hydroxylating monooxygenase (PHM) contains <scene name='Journal:JBIC:17/Cv/4'>two non-equivalent copper sites (CuH and CuM)</scene>. CuM serves as an oxygen binding and hydrogen abstraction site, CuH is involved in electron transfer. In the structure of Cu(II)-PHM complexed with hydrogen peroxide determined to 1.98 Å resolution, <scene name='Journal:JBIC:17/Cv/7'>(hydro)peroxide binds exclusively to CuM in a slightly asymmetric side-on mode</scene>. The <scene name='Journal:JBIC:17/Cv/8'>interatomic O-O distance of the copper-bound ligand is 1.5, characteristic of peroxide/hydroperoxide species, and the copper-oxygen distances are 2.0 and 2.1</scene> Å. This Cu(II)-bound <scene name='Journal:JBIC:17/Cv/9'>peroxo moiety interacts closely with a molecule of water</scene>, forming <scene name='Journal:JBIC:17/Cv/10'>hydrogen bonds that stabilize the structure</scene>. DFT and QM/MM calculations indicate that this species is a Cu-bound doubly deprotonated peroxidate and that its energy is similar to that of its isomer Cu(I)-bound superoxide.
-
</StructureSection>
 
==3D structures of monooxygenase==
==3D structures of monooxygenase==
 +
[[Monooxygenase 3D structures]]
-
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
+
</StructureSection>
-
{{#tree:id=OrganizedByTopic|openlevels=0|
+
-
 
+
-
*'''Toluene 4-monooxygenase (TMO)'''
+
-
 
+
-
**[[3dhg]], [[3i5j]], [[2inc]] – PmTMO α+β+γ subunits + Fe – ''Pseudomonas mendocina''<br />
+
-
**[[2ind]] – PmTMO α+β+γ subunits + Mn <br />
+
-
**[[3rng]], [[3rnf]], [[3rne]], [[3rnc]], [[3rnb]], [[3rna]], [[3rn9]], [[3n20]], [[3n1z]], [[3n1y]], [[3n1x]], [[2rdb]] – PmTMO α+β+γ subunits (mutant) + Fe <br />
+
-
**[[1sjg]] – PmTMO protein C + Fe <br />
+
-
**[[1vm9]] – PmTMO protein C (mutant) + Fe <br />
+
-
**[[2bf5]], [[2bf3]], [[2bf2]] – PmTMO protein D <br />
+
-
**[[4wqm]] – PmTMO (mutant) + Ni <br />
+
-
**[[4p1c]], [[4p1b]] – PmTMO protein A+B+E+ferredoxin (mutant) + Fe <br />
+
-
**[[2q3w]] – PmTMO ferredoxin subunit (mutant) + Fe <br />
+
-
 
+
-
*TMO complexes
+
-
 
+
-
**[[3dhh]], [[3q3n]], [[3q3o]] – PmTMO α+β+γ subunits + Fe + phenol derivative + TMO system effector protein<br />
+
-
**[[3rmk]], [[1t0s]], [[1t0q]] – PmTMO α+β+γ subunits + Fe + phenol derivative<br />
+
-
**[[3q14]] – PmTMO α+β+γ subunits + Fe + p-cresol + TMO system effector protein<br />
+
-
**[[3q2a]], [[3q3m]] – PmTMO α+β+γ subunits + Fe + benzoate inhibitor + TMO system effector protein<br />
+
-
**[[3dhi]] – PmTMO α+β+γ subunits + Fe + TMO system effector protein<br />
+
-
**[[3ge3]], [[3ge8]], [[3ri7]] – PmTMO α (mutant)+β+γ subunits + Fe + TMO system effector protein<br />
+
-
**[[3i63]] – PmTMO α+β+γ subunits + Fe + TMO system effector protein + H2O2<br />
+
-
**[[5tdv]] – PmTMO protein A+B+D+E + Fe + peroxide<br />
+
-
**[[5tdu]] – PmTMO protein A+B+D+E + Fe + cresol<br />
+
-
**[[5tdt]] – PmTMO protein A+B+D+E + Fe + peroxide + toluene<br />
+
-
**[[5tds]] – PmTMO protein A+B+D+E + Fe + toluene<br />
+
-
**[[1t0r]] – PsTMO + Fe + OH – ''Pseudomonas stutzeri''<br />
+
-
 
+
-
*'''Heme-degrading monooxygenase (IsdI)'''
+
-
 
+
-
**[[2zdp]] – SaIsdI + heme-Co – ''Staphylococcus aureus''<br />
+
-
**[[3lgm]], [[2zdo]] – SaIsdI + heme-Fe<br />
+
-
**[[4fnh]] – SaIsdI (mutant) + heme-Fe<br />
+
-
**[[3lgn]] – SaIsdI + heme-Fe + O2<br />
+
-
**[[3qgp]] – SaIsdI + heme-Fe + CN<br />
+
-
**[[4fni]] – SaIsdI (mutant) + heme-Fe + CN<br />
+
-
**[[4nl5]] – MtMO + heme + CN – ''Mycobacterium tuberculosis''<br />
+
-
**[[4oz5]] – MO + heme – ''Bacillus subtilis''<br />
+
-
 
+
-
*'''Kynurenine 3-monooxygenase (KMO)'''
+
-
 
+
-
**[[4j2w]], [[4j31]], [[4j33]], [[4j34]] – yKMO + FAD – yeast<br />
+
-
**[[4j36]] – yKMO + FAD + inhibitor<br />
+
-
**[[5na5]] – PfKMO (mutant) + FAD – ''Pseudomonas fluorescens''<br />
+
-
**[[5nak]] – PfKMO (mutant) + FAD + kynurenine <br />
+
-
**[[5nah]], [[5nag]], [[5nae]], [[5nab]], [[5n7t]], [[5mzk]], [[5mzi]], [[5mzc]], [[5fn0]] – PfKMO (mutant) + FAD + inhibitor<br />
+
-
 
+
-
*'''Phenol 2-monooxygenase (PMO)'''
+
-
 
+
-
**[[1foh]] – TcPMO + FAD – ''Trichosporon cutaneum''<br />
+
-
**[[1pn0]] – TcPMO + FAD + phenol<br />
+
-
 
+
-
*'''Phenylalanine 2-monooxygenase'''
+
-
 
+
-
**[[5pah]], [[6pah]]. – FMO catalytic domain + inhibitor – human<br />
+
-
 
+
-
*'''ActVA-Orf6 monooxygenase (AOMO)'''
+
-
 
+
-
**[[1lq9]] – ScAOMO – ''Streptomyces coelicolor''<br />
+
-
**[[1n5q]] – ScAOMO + sancycline <br />
+
-
**[[1n5s]], [[1n5t]] – ScAOMO + acetyl dithranol<br />
+
-
**[[1n5v]] – ScAOMO + nanaomycine <br />
+
-
 
+
-
*'''Flavin-containing monooxygenase'''
+
-
 
+
-
**[[2gv8]] – fyMO + FAD + NADP – fission yeast<br />
+
-
**[[2gvc]] – fyMO + FAD + NADP + methimazole<br />
+
-
**[[4a9w]] – SmMO + FAD – ''Stenotrophomonas maltophilia''<br />
+
-
**[[4c5o]] – SmMO (mutant) + FAD <br />
+
-
**[[5wan]] – MO + FMN + uracil – Escherichia coli<br />
+
-
**[[5iq4]], [[5iq1]], [[5ipy]] – RnMO (mutant) + FAD + NAP – ''Roseovarius nubinhibens'' <br />
+
-
**[[5gsn]] – RnMO (mutant) + FAD + NAP + methimazole <br />
+
-
**[[4usr]] – PsMO + FAD <br />
+
-
**[[3rp6]] – KpMO + FAD – ''Klebsiella pneumoniae''<br />
+
-
**[[3rp8]] – KpMO (mutant) + FAD <br />
+
-
**[[3rp7]] – KpMO + FAD + uric acid<br />
+
-
**[[3c96]], [[2rgj]] – PaMO + FAD – ''Pseudomonas aeruginosa''<br />
+
-
**[[2xvf]], [[2xve]] – MaMO + FAD – ''Methylophaga aminisulfidivorans'' <br />
+
-
**[[2xvj]] – MaMO (mutant) + FAD + indole <br />
+
-
**[[2xvi]] – MaMO (mutant) + FAD + O2<br />
+
-
**[[2vqb]] – MaMO (mutant) + FAD + NADP + O2<br />
+
-
**[[2xvh]], [[2xlu]], [[2xlt]] – MaMO + FAD + NADP derivative<br />
+
-
**[[2xls]], [[2xlr]], [[2xlp]], [[2vq7]] – MaMO (mutant) + FAD + NADP <br />
+
-
 
+
-
*Pentachlorophenol 4-monooxygenase
+
-
 
+
-
**[[5kox]] – NfMO + FAD – ''Nocardia farcinica''<br />
+
-
**[[5kox]] – NfMO + FAD + rifampicin <br />
+
-
 
+
-
*2,4,6-trichlorophenol 4-monooxygenase
+
-
 
+
-
**[[4g5e]] – MO – ''Cupriavidus necator''<br />
+
-
 
+
-
*Chlorophenol 4-monooxygenase
+
-
 
+
-
**[[4oo2]] – MO – ''Streptomyces globisporus''<br />
+
-
**[[3k86]], [[3hwc]] – BcMO – ''Burkholderia cepacia'' <br />
+
-
**[[3k87]] – BcMO + FAD <br />
+
-
**[[3k88]] – BcMO + FAD + NAD <br />
+
-
 
+
-
*Phenylacetone monooxygenase
+
-
 
+
-
**[[4ovi]], [[4c74]] – TfMO + FAD + APADP – ''Thermobifida fusca''<br />
+
-
**[[1w4x]] – TfMO + FAD<br />
+
-
**[[2ylt]], [[2yls]], [[2ylr]] – TfMO + FAD + NADP <br />
+
-
**[[2ylz]] – TfMO (mutant) + FAD <br />
+
-
**[[4c77]] – TfMO (mutant) + FAD + APADP <br />
+
-
**[[4d04]] – TfMO (mutant) + FAD + NAP <br />
+
-
**[[4d03]], [[2ym2]], [[2ylx]], [[2ylw]] – TfMO (mutant) + FAD + NADP <br />
+
-
**[[2ym1]] – TfMO (mutant) + FAD + NADP + O2<br />
+
-
 
+
-
*6-hydroxynicotinate 3-monooxygenase
+
-
 
+
-
**[[5eow]] – PpMO + FAD – ''Pseudomonas putida''<br />
+
-
 
+
-
*Styrene monooxygenase
+
-
 
+
-
**[[3ihm]] – PpMO <br />
+
-
**[[4f07]] – PpMO (mutant) + FAD <br />
+
-
 
+
-
*Tryptophan 2-monooxygenase
+
-
 
+
-
**[[4iv9]] – MO + FAD – ''Pseudomonas savastanoi''<br />
+
-
 
+
-
*Tryptophan 5-monooxygenase
+
-
 
+
-
**[[1mlw]] – hMO + Fe + dihydrobiopterin <br />
+
-
 
+
-
*Tyrosine 3-monooxygenase
+
-
 
+
-
**[[2xsn]] – hMO + Zn<br />
+
-
**[[2toh]] – rMO + Fe + dihydrobiopterin + tyrosine - rat<br />
+
-
**[[2mda]] – rMO regulatory domain <br />
+
-
 
+
-
*Nitronate monooxygenase
+
-
 
+
-
**[[4q4k]] – PaMO + FMN <br />
+
-
**[[5lsm]] – MO + FMN – ''Shewanella oneidensis''<br />
+
-
 
+
-
*2-hydroxbiphenyl 3-monooxygenase
+
-
 
+
-
**[[4z2r]] – PnMO + FAD – ''Pseudomonas nitroreducens''<br />
+
-
**[[4cy6]] – PnMO (mutant) <br />
+
-
**[[4z2u]], [[4z2t]], [[4cy8]] – PnMO (mutant) + FAD <br />
+
-
**[[5brt]] – PnMO + FAD + hydroxybephenyl <br />
+
-
 
+
-
*4-hydroxyphenylacetate 3-monooxygenase
+
-
 
+
-
**[[4ira]] – BmMO + FAD – Brucella melitensis<br />
+
-
**[[3cb0]] – BmMO + FMN<br />
+
-
 
+
-
*Ornithine N(5)-monooxygenase
+
-
 
+
-
**[[5cku]] – MO + FAD + NADP + ornithine – ''Neosartorya fumigata''<br />
+
-
**[[4nzh]], [[4b69]] – AfMO + FAD + ornithine – ''Aspergillus fumigatus''<br />
+
-
**[[4b65]] – AfMO + FAD + NADP <br />
+
-
**[[4b68]], [[4b66]] – AfMO + FAD + NAP + arginine <br />
+
-
**[[4b67]], [[4b63]] – AfMO + FAD + NADP + ornithine <br />
+
-
**[[4b64]] – AfMO + FAD + NADP + lysine <br />
+
-
**[[3s61]] – PaMO + FAD + NADP + ornithine derivative<br />
+
-
 
+
-
*Steroid monooxygenase
+
-
 
+
-
**[[4ap1]], [[4aos]] – RrMO + FAD + NADP – ''Rhodococcus rhodochrous''<br />
+
-
**[[4aox]] – RrMO (mutant) + FAD <br />
+
-
**[[4ap3]] – RrMO (mutant) + FAD + NADP <br />
+
-
 
+
-
*Cyclohexanone monooxygenase
+
-
 
+
-
**[[5m10]] – TmMO + FAD + NAP + nicotinamide – ''Thermocripsum municipale''''Italic text''<br />
+
-
**[[5m0z]] – TmMO + FAD + NADP derivative <br />
+
-
**[[4rg4]], [[4rg3]], [[3gwf]], [[3gwd]] – RhMO + FAD + NAP + caprolactone – ''Rhodococcus''<br />
+
-
**[[3ucl]] – RhMO + FAD + NADP + cyclohexanone <br />
+
-
 
+
-
*Lysine 6-monooxygenase
+
-
 
+
-
**[[5cqf]] – MO – ''Pseudomonas syringae''<br />
+
-
**[[4d7e]] – MO (mutant) + FAD – ''Nocardia farcinica''<br />
+
-
 
+
-
*EDTA monooxygenase
+
-
 
+
-
**[[5dqp]] – MO – ''Chelativorans''<br />
+
-
 
+
-
*3,6-diketocamphane 1,6 monooxygenase
+
-
 
+
-
**[[5aec]] – PpMO <br />
+
-
**[[4uwm]] – PpMO + FMN<br />
+
-
 
+
-
*Lytic polysaccharide monooxygenase
+
-
 
+
-
**[[5tki]], [[5foh]], [[4qi8]] – NcMO-2 + Cu – ''Neurospora crassa''''Italic text''<br />
+
-
**[[5tkh]], [[5tkg]], [[5tkf]], [[4eir]] – NcMO-2 + Cu + O2 <br />
+
-
**[[4eis]] – NcMO-3 + Cu + peroxide <br />
+
-
**[[5iju]] – MO + Cu – ''Bacillus amyloliquefaciens''<br />
+
-
**[[5acj]], [[5aci]], [[5ach]], [[5acg]], [[5acf]] – MO + Cu – ''Lentinus similis''<br />
+
-
**[[4mai]] – moMO + Cu – mold<br />
+
-
**[[4mah]] – moMO + Zn<br />
+
-
 
+
-
*Peptidyl-glycine alpha-amidating monooxygenase
+
-
 
+
-
**[[3mib]], [[3mic]], [[3mid]], [[3mie]], [[3mif]], [[3mig]], [[3mih]], [[3mlj]], [[3mlk]], [[3mll]], [[1opm]] – rMO + Cu + Ni <br />
+
-
**[[1sdw]] – rMO + Cu + Ni + O2 + threonine derivative<br />
+
-
**[[1yjl]] – rMO (mutant)<br />
+
-
**[[1yjk]], [[1yip]], [[1phm]] – rMO + Cu<br />
+
-
**[[1yi9]] – rMO (mutant) + Cu<br />
+
-
**[[3fw0]] – rMO + Hg<br />
+
-
**[[3fvz]] – rMO + Zn + Fe<br />
+
-
 
+
-
*Antibiotic biosynthesis monooxygenase
+
-
 
+
-
**[[4hl9]] – MO – ''Rhodospirillum rubrum''<br />
+
-
**[[4dn9]] – MO – ''Chloroflexus aurantiacus''<br />
+
-
**[[2ril]] – MO – ''Shewanella loihica''<br />
+
-
 
+
-
*Monooxygenase
+
-
 
+
-
**[[2i7g]] – MO – ''Agrobacterium tumefaciens''<br />
+
-
**[[5uq4]] – MtMO <br />
+
-
**[[5f5l]] – MiMO – ''Micromonospora'' <br />
+
-
**[[5f5n]] – MiMO + NAD + substrate <br />
+
-
 
+
-
'''Methane monooxygenase''' See [[Methane monooxygenase]]
+
-
 
+
-
'''Camphor 5-monooxygenase''' See [[Cytochrome P450]]
+
-
 
+
-
'''Luciferin 4-monooxygenase and Alkanal monooxygenase''' See [[Luciferase]]
+
-
}}
+
== References ==
== References ==

Current revision

Glycosylated lytic polysaccharide monooxygenase complex with Cu(II) (orange) and peroxide (PDB code 5tkh)

Drag the structure with the mouse to rotate

References

  1. ↑ Sciara G, Kendrew SG, Miele AE, Marsh NG, Federici L, Malatesta F, Schimperna G, Savino C, Vallone B. The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis. EMBO J. 2003 Jan 15;22(2):205-15. PMID:12514126 doi:http://dx.doi.org/10.1093/emboj/cdg031
  2. ↑ Fraaije MW, Wu J, Heuts DP, van Hellemond EW, Spelberg JH, Janssen DB. Discovery of a thermostable Baeyer-Villiger monooxygenase by genome mining. Appl Microbiol Biotechnol. 2005 Jan;66(4):393-400. PMID:15599520 doi:10.1007/s00253-004-1749-5
  3. ↑ Benitez AR, Tweedy S, Baker Dockrey SA, Lukowski AL, Wymore T, Khare D, Brooks CL 3rd, Palfey BA, Smith JL, Narayan ARH. Structural basis for selectivity in flavin-dependent monooxygenase-catalyzed oxidative dearomatization. ACS Catal. 2019 Apr 5;9(4):3633-3640. doi: 10.1021/acscatal.8b04575. Epub 2019, Mar 25. PMID:31346489 doi:http://dx.doi.org/10.1021/acscatal.8b04575
  4. ↑ Yang W, Moore IF, Koteva KP, Bareich DC, Hughes DW, Wright GD. TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline antibiotics. J Biol Chem. 2004 Dec 10;279(50):52346-52. doi: 10.1074/jbc.M409573200. Epub 2004, Sep 27. PMID:15452119 doi:http://dx.doi.org/10.1074/jbc.M409573200
  5. ↑ Rudzka K, Moreno DM, Eipper B, Mains R, Estrin DA, Amzel LM. Coordination of peroxide to the Cu(M) center of peptidylglycine alpha-hydroxylating monooxygenase (PHM): structural and computational study. J Biol Inorg Chem. 2012 Dec 18. PMID:23247335 doi:10.1007/s00775-012-0967-z

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman, Alexander Berchansky, Jaime Prilusky

Retrieved from "http://52.214.119.220/wiki/index.php/Monooxygenase"
Personal tools