Monooxygenase

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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.
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==3D structures of monooxygenase==
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[[Monooxygenase 3D structures]]
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</StructureSection>
</StructureSection>
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*'''Kynurenine 3-monooxygenase (KMO)'''
*'''Kynurenine 3-monooxygenase (KMO)'''
 +
**[[5x68]] – hKMO + FAD - human<br />
**[[4j2w]], [[4j31]], [[4j33]], [[4j34]] – yKMO + FAD – yeast<br />
**[[4j2w]], [[4j31]], [[4j33]], [[4j34]] – yKMO + FAD – yeast<br />
**[[4j36]], [[5x64]] – yKMO + FAD + inhibitor<br />
**[[4j36]], [[5x64]] – yKMO + FAD + inhibitor<br />
**[[5x6q]] – yKMO (mutant) + FAD + inhibitor<br />
**[[5x6q]] – yKMO (mutant) + FAD + inhibitor<br />
-
**[[5x68]] – hKMO + FAD - human<br />
 
**[[5na5]], [[5x6p]] – PfKMO (mutant) + FAD – ''Pseudomonas fluorescens''<br />
**[[5na5]], [[5x6p]] – PfKMO (mutant) + FAD – ''Pseudomonas fluorescens''<br />
-
**[[5y7a]], [[5y77]] – PfKMO + FAD + kynurenine <br />
+
**[[5y7a]], [[5y77]], [[6fox]] – PfKMO + FAD + kynurenine <br />
**[[5nak]] – PfKMO (mutant) + FAD + kynurenine <br />
**[[5nak]] – PfKMO (mutant) + FAD + kynurenine <br />
**[[5y66]] – PfKMO + FAD + kynurenine + inhibitor<br />
**[[5y66]] – PfKMO + FAD + kynurenine + inhibitor<br />
 +
**[[6fph]], [[6fp1]], [[6fp0]], [[6foz]], [[6foy]] – PfKMO + FAD + inhibitor<br />
**[[5nah]], [[5nag]], [[5nae]], [[5nab]], [[5n7t]], [[5mzk]], [[5mzi]], [[5mzc]], [[5fn0]] – PfKMO (mutant) + FAD + inhibitor<br />
**[[5nah]], [[5nag]], [[5nae]], [[5nab]], [[5n7t]], [[5mzk]], [[5mzi]], [[5mzc]], [[5fn0]] – PfKMO (mutant) + FAD + inhibitor<br />
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**[[5pah]], [[6pah]] – hFMO catalytic domain + inhibitor <br />
**[[5pah]], [[6pah]] – hFMO catalytic domain + inhibitor <br />
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*Phenylalanine 4-monooxygenase or phenylalanine-4-hydroxylase
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See [[Hydroxylase]]
*'''ActVA-Orf6 monooxygenase (AOMO)'''
*'''ActVA-Orf6 monooxygenase (AOMO)'''
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**[[1n5s]], [[1n5t]] – ScAOMO + acetyl dithranol<br />
**[[1n5s]], [[1n5t]] – ScAOMO + acetyl dithranol<br />
**[[1n5v]] – ScAOMO + nanaomycine <br />
**[[1n5v]] – ScAOMO + nanaomycine <br />
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*Baeyer-Villiger monooxygenase (BVMO)
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**[[6jdk]] – BVMO – ''Parvibaculum lavamentivorans''<br />
*'''Flavin-containing monooxygenase'''
*'''Flavin-containing monooxygenase'''
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**[[4a9w]] – SmMO + FAD – ''Stenotrophomonas maltophilia''<br />
**[[4a9w]] – SmMO + FAD – ''Stenotrophomonas maltophilia''<br />
**[[4c5o]] – SmMO (mutant) + FAD <br />
**[[4c5o]] – SmMO (mutant) + FAD <br />
-
**[[5wan]] – MO + FMN + uracil – Escherichia coli<br />
+
**[[5wan]] – EcMO + FMN + uracil – Escherichia coli<br />
**[[5iq4]], [[5iq1]], [[5ipy]] – RnMO (mutant) + FAD + NAP – ''Roseovarius nubinhibens'' <br />
**[[5iq4]], [[5iq1]], [[5ipy]] – RnMO (mutant) + FAD + NAP – ''Roseovarius nubinhibens'' <br />
**[[5gsn]] – RnMO (mutant) + FAD + NAP + methimazole <br />
**[[5gsn]] – RnMO (mutant) + FAD + NAP + methimazole <br />
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**[[4q4k]] – PaMO + FMN <br />
**[[4q4k]] – PaMO + FMN <br />
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**[[6e2a]] – PaMO + FMN + NAD<br />
**[[5lsm]] – MO + FMN – ''Shewanella oneidensis''<br />
**[[5lsm]] – MO + FMN – ''Shewanella oneidensis''<br />
**[[6bka]] – MO + FMN – ''Cyberlyndnera mrakii''<br />
**[[6bka]] – MO + FMN – ''Cyberlyndnera mrakii''<br />
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*4-hydroxyphenylacetate 3-monooxygenase
*4-hydroxyphenylacetate 3-monooxygenase
-
**[[4ira]] – BmMO + FAD – Brucella melitensis<br />
+
**[[4ira]] – BmMO + FAD – ''Brucella melitensis''<br />
**[[3cb0]] – BmMO + FMN<br />
**[[3cb0]] – BmMO + FMN<br />
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**[[6eb0]] – EcMO oxygenase subunit<br />
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**[[6b1b]] – EcMO oxygenase subunit (mutant)<br />
*Ornithine N(5)-monooxygenase
*Ornithine N(5)-monooxygenase
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*Cyclohexanone monooxygenase
*Cyclohexanone monooxygenase
-
**[[5m10]] – TmMO + FAD + NAP + nicotinamide – ''Thermocripsum municipale''''Italic text''<br />
+
**[[5m10]] – TmMO + FAD + NAP + nicotinamide – ''Thermocripsum municipale''<br />
**[[5m0z]] – TmMO + FAD + NADP derivative <br />
**[[5m0z]] – TmMO + FAD + NADP derivative <br />
-
**[[4rg4]], [[4rg3]], [[3gwf]], [[3gwd]] – RhMO + FAD + NAP + caprolactone – ''Rhodococcus''<br />
+
**[[6gqi]] – TmMO + FAD + NADP + hexanic acid <br />
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**[[6era]], [[6er9]] – RhMO + FAD + NADP – ''Rhodococcus''<br />
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**[[4rg4]], [[4rg3]], [[3gwf]], [[3gwd]] – RhMO + FAD + NAP + caprolactone <br />
**[[3ucl]] – RhMO + FAD + NADP + cyclohexanone <br />
**[[3ucl]] – RhMO + FAD + NADP + cyclohexanone <br />
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**[[5mw0]], [[5wkw]] – rMO <br />
**[[5mw0]], [[5wkw]] – rMO <br />
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**[[1yjl]] – rMO (mutant)<br />
**[[3mib]], [[3mic]], [[3mid]], [[3mie]], [[3mif]], [[3mig]], [[3mih]], [[3mlj]], [[3mlk]], [[3mll]], [[1opm]] – rMO + Cu + Ni <br />
**[[3mib]], [[3mic]], [[3mid]], [[3mie]], [[3mif]], [[3mig]], [[3mih]], [[3mlj]], [[3mlk]], [[3mll]], [[1opm]] – rMO + Cu + Ni <br />
 +
**[[6ao6]], [[5wja]] – rMO (mutant) + Cu + Ni<br />
**[[1sdw]] – rMO + Cu + Ni + O2 + threonine derivative<br />
**[[1sdw]] – rMO + Cu + Ni + O2 + threonine derivative<br />
-
**[[1yjl]] – rMO (mutant)<br />
 
**[[1yjk]], [[1yip]], [[1phm]] – rMO + Cu<br />
**[[1yjk]], [[1yip]], [[1phm]] – rMO + Cu<br />
**[[1yi9]], [[6ay0]], [[6an3]], [[6amp]], [[6alv]], [[6ala]] – rMO (mutant) + Cu<br />
**[[1yi9]], [[6ay0]], [[6an3]], [[6amp]], [[6alv]], [[6ala]] – rMO (mutant) + Cu<br />
-
**[[6ao6]], [[5wja]] – rMO (mutant) + Cu + Ni<br />
 
**[[3fw0]] – rMO + Hg<br />
**[[3fw0]] – rMO + Hg<br />
**[[3fvz]] – rMO + Zn + Fe<br />
**[[3fvz]] – rMO + Zn + Fe<br />
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**[[5f5l]] – MiMO – ''Micromonospora'' <br />
**[[5f5l]] – MiMO – ''Micromonospora'' <br />
**[[5f5n]] – MiMO + NAD + substrate <br />
**[[5f5n]] – MiMO + NAD + substrate <br />
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*Monooxygenase TROPB
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**[[6nes]] – TsMO + FAD – ''Talaromyces stipitatus''<br />
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**[[6nev]], [[6neu]] – TsMO (mutant) + FAD <br />
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**[[6net]] – TsMO + FAD + dihydroxy dimethylbenzaldehyde<br />
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*Lactate 2-monooxygenase or lactate oxydase
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**[[6dvi]] – MsLMO + FMN – ''Mycobacterium smegmatis''<br />
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**[[6dvh]] – MsLMO (mutant) + FMN <br />
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*Squalene monooxygenase or squalene epoxidase
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**[[6c6r]], [[6c6p]], [[6c6n]] – hSMO + FAD + inhibitor<br />
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*Dimethyl-sulfide monooxygenase
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**[[6ak1]] – DMOA – ''Hyphomicrobium sulfonivorans''<br />
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*Salicylate 1-monooxygenase or salicylate hydroxylase
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See [[Hydroxylase]]
'''Methane monooxygenase''' See [[Methane monooxygenase]]
'''Methane monooxygenase''' See [[Methane monooxygenase]]

Revision as of 11:10, 3 November 2019

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

Drag the structure with the mouse to rotate

3D structures of monooxygenase

Updated on 03-November-2019

See Hydroxylase

See Hydroxylase

Methane monooxygenase See Methane monooxygenase

Camphor 5-monooxygenase See Cytochrome P450

Luciferin 4-monooxygenase and Alkanal monooxygenase See Luciferase

References

  1. ↑ 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

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