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PDBsum entry 1n5q

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1n5q
Jmol
Contents
Protein chains
112 a.a. *
Ligands
P6G
TNC
Waters ×179
* Residue conservation analysis
PDB id:
1n5q
Name: Oxidoreductase
Title: Crystal structure of a monooxygenase from the gene actva-orf streptomyces coelicolor in complex with dehydrated sancycli
Structure: Actava-orf6 monooxygenase. Chain: a, b. Engineered: yes
Source: Streptomyces coelicolor. Organism_taxid: 100226. Strain: a3(2). Gene: actva-orf6. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.74Å     R-factor:   0.190     R-free:   0.240
Authors: G.Sciara,S.G.Kendrew,A.E.Miele,N.G.Marsh,L.Federici,F.Malate G.Schimperna,C.Savino,B.Vallone
Key ref:
G.Sciara et al. (2003). The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis. EMBO J, 22, 205-215. PubMed id: 12514126 DOI: 10.1093/emboj/cdg031
Date:
07-Nov-02     Release date:   14-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q53908  (Q53908_STRCH) -  ActVA 6 protein
Seq:
Struc:
113 a.a.
112 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1093/emboj/cdg031 EMBO J 22:205-215 (2003)
PubMed id: 12514126  
 
 
The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis.
G.Sciara, S.G.Kendrew, A.E.Miele, N.G.Marsh, L.Federici, F.Malatesta, G.Schimperna, C.Savino, B.Vallone.
 
  ABSTRACT  
 
ActVA-Orf6 monooxygenase from Streptomyces coelicolor that catalyses the oxidation of an aromatic intermediate of the actinorhodin biosynthetic pathway is a member of a class of small monooxygenases that carry out oxygenation without the assistance of any of the prosthetic groups, metal ions or cofactors normally associated with activation of molecular oxygen. The overall structure is a ferredoxin-like fold with a novel dimeric assembly, indicating that the widely represented ferredoxin fold may sustain yet another functionality. The resolution (1.3 A) of the enzyme structure and its complex with substrate and product analogues allows us to visualize the mechanism of binding and activation of the substrate for attack by molecular oxygen, and utilization of two gates for the reaction components including a proton gate and an O(2)/H(2)O gate with a putative protein channel. This is the first crystal structure of an enzyme involved in the tailoring of a type II aromatic polyketide and illustrates some of the enzyme-substrate recognition features that may apply to a range of other enzymes involved in modifying a polyketide core structure.
 
  Selected figure(s)  
 
Figure 6.
Figure 6 Putative catalytic mechanism of ActVA-Orf6 monooxygenase. Once 6-DDHK (shown here with alternative tautomeric form) enters the active site, stabilization of intramolecular hydrogen bonds (A) is associated with H+ transfer to Tyr72 (B) to yield the deprotonated form. C-6 carbanion can react with molecular oxygen (C). This leads to a peroxy intermediate (D), stabilized by hydrogen bonds with Asn62 and Tyr51. Protonation followed by dehydration is then necessary to complete the reaction.
Figure 7.
Figure 7 Hypothetical peroxy intermediate built on the atomic coordinates of acetyl dithranol in the active site B of ActVA-Orf6 monooxygenase. The model assumes sp3 geometry for the reactive carbon C-6. Asn62 and Tyr51 are in favourable stereochemistry to stabilize such an intermediate by hydrogen bonding.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2003, 22, 205-215) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21102601 F.Kudo, T.Yonezawa, A.Komatsubara, K.Mizoue, and T.Eguchi (2011).
Cloning of the biosynthetic gene cluster for naphthoxanthene antibiotic FD-594 from Streptomyces sp. TA-0256.
  J Antibiot (Tokyo), 64, 123-132.  
  21491497 L.Gabison, C.Chopard, N.Colloc'h, F.Peyrot, B.Castro, M.E.Hajji, M.Altarsha, G.Monard, M.Chiadmi, and T.Prangé (2011).
X-ray, ESR, and quantum mechanics studies unravel a spin well in the cofactor-less urate oxidase.
  Proteins, 79, 1964-1976.
PDB code: 3obp
20352666 C.Olano, C.Méndez, and J.A.Salas (2010).
Post-PKS tailoring steps in natural product-producing actinomycetes from the perspective of combinatorial biosynthesis.
  Nat Prod Rep, 27, 571-616.  
19926290 H.X.Zhou, and J.A.McCammon (2010).
The gates of ion channels and enzymes.
  Trends Biochem Sci, 35, 179-185.  
20348292 K.C.Ehrlich, P.Li, L.Scharfenstein, and P.K.Chang (2010).
HypC, the anthrone oxidase involved in aflatoxin biosynthesis.
  Appl Environ Microbiol, 76, 3374-3377.  
19917297 N.Chim, A.Iniguez, T.Q.Nguyen, and C.W.Goulding (2010).
Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis.
  J Mol Biol, 395, 595-608.
PDB code: 3hx9
20080731 R.A.Steiner, H.J.Janssen, P.Roversi, A.J.Oakley, and S.Fetzner (2010).
Structural basis for cofactor-independent dioxygenation of N-heteroaromatic compounds at the alpha/beta-hydrolase fold.
  Proc Natl Acad Sci U S A, 107, 657-662.
PDB codes: 2wj3 2wj4 2wj6 2wm2 3ibt
20157809 S.Fetzner, and R.A.Steiner (2010).
Cofactor-independent oxidases and oxygenases.
  Appl Microbiol Biotechnol, 86, 791-804.  
  19255477 H.Koskiniemi, T.Grocholski, G.Schneider, and J.Niemi (2009).
Expression, purification and crystallization of the cofactor-independent monooxygenase SnoaB from the nogalamycin biosynthetic pathway.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 256-259.  
19801657 M.Marín, D.W.Heinz, D.H.Pieper, and B.U.Klink (2009).
Crystal structure and catalytic mechanism of 4-methylmuconolactone methylisomerase.
  J Biol Chem, 284, 32709-32716.
PDB codes: 3hds 3hf5 3hfk
17729271 H.J.Cho, K.J.Kim, M.H.Kim, and B.S.Kang (2008).
Structural insight of the role of the Hahella chejuensis HapK protein in prodigiosin biosynthesis.
  Proteins, 70, 257-262.
PDB code: 2jdj
18375516 N.Colloc'h, L.Gabison, G.Monard, M.Altarsha, M.Chiadmi, G.Marassio, J.Sopkova-de Oliveira Santos, M.El Hajji, B.Castro, J.H.Abraini, and T.Prangé (2008).
Oxygen pressurized X-ray crystallography: probing the dioxygen binding site in cofactorless urate oxidase and implications for its catalytic mechanism.
  Biophys J, 95, 2415-2422.
PDB codes: 2zka 2zkb 3cks 3cku
18291320 P.Kallio, Z.Liu, P.Mäntsälä, J.Niemi, and M.Metsä-Ketelä (2008).
Sequential action of two flavoenzymes, PgaE and PgaM, in angucycline biosynthesis: chemoenzymatic synthesis of gaudimycin C.
  Chem Biol, 15, 157-166.  
18954462 T.A.Binkowski, and A.Joachimiak (2008).
Protein functional surfaces: global shape matching and local spatial alignments of ligand binding sites.
  BMC Struct Biol, 8, 45.  
18940666 T.Oja, K.Palmu, H.Lehmussola, O.Leppäranta, K.Hännikäinen, J.Niemi, P.Mäntsälä, and M.Metsä-Ketelä (2008).
Characterization of the alnumycin gene cluster reveals unusual gene products for pyran ring formation and dioxan biosynthesis.
  Chem Biol, 15, 1046-1057.  
18713745 W.C.Lee, M.L.Reniere, E.P.Skaar, and M.E.Murphy (2008).
Ruffling of Metalloporphyrins Bound to IsdG and IsdI, Two Heme-degrading Enzymes in Staphylococcus aureus.
  J Biol Chem, 283, 30957-30963.
PDB codes: 2zdo 2zdp
18070976 X.Zhang, L.B.Alemany, H.P.Fiedler, M.Goodfellow, and R.J.Parry (2008).
Biosynthetic investigations of lactonamycin and lactonamycin z: cloning of the biosynthetic gene clusters and discovery of an unusual starter unit.
  Antimicrob Agents Chemother, 52, 574-585.  
17668295 A.Matte, Z.Jia, S.Sunita, J.Sivaraman, and M.Cygler (2007).
Insights into the biology of Escherichia coli through structural proteomics.
  J Struct Funct Genomics, 8, 45-55.  
17722122 A.O.Brachmann, S.A.Joyce, H.Jenke-Kodama, G.Schwär, D.J.Clarke, and H.B.Bode (2007).
A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens.
  Chembiochem, 8, 1721-1728.  
17268612 C.Hertweck, A.Luzhetskyy, Y.Rebets, and A.Bechthold (2007).
Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork.
  Nat Prod Rep, 24, 162-190.  
17639604 M.A.Adams, M.D.Suits, J.Zheng, and Z.Jia (2007).
Piecing together the structure-function puzzle: experiences in structure-based functional annotation of hypothetical proteins.
  Proteomics, 7, 2920-2932.  
17387580 M.L.Reniere, V.J.Torres, and E.P.Skaar (2007).
Intracellular metalloporphyrin metabolism in Staphylococcus aureus.
  Biometals, 20, 333-345.  
17283083 M.S.Oakley, S.Kumar, V.Anantharaman, H.Zheng, B.Mahajan, J.D.Haynes, J.K.Moch, R.Fairhurst, T.F.McCutchan, and L.Aravind (2007).
Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites.
  Infect Immun, 75, 2012-2025.  
17507985 P.F.Widboom, E.N.Fielding, Y.Liu, and S.D.Bruner (2007).
Structural basis for cofactor-independent dioxygenation in vancomycin biosynthesis.
  Nature, 447, 342-345.
PDB code: 2np9
17576423 S.Fetzner (2007).
Cofactor-independent oxygenases go it alone.
  Nat Chem Biol, 3, 374-375.  
17158935 X.Zhang, and R.J.Parry (2007).
Cloning and characterization of the pyrrolomycin biosynthetic gene clusters from Actinosporangium vitaminophilum ATCC 31673 and Streptomyces sp. strain UC 11065.
  Antimicrob Agents Chemother, 51, 946-957.  
16403788 E.Bab-Dinitz, H.Shmuely, J.Maupin-Furlow, J.Eichler, and B.Shaanan (2006).
Haloferax volcanii PitA: an example of functional interaction between the Pfam chlorite dismutase and antibiotic biosynthesis monooxygenase families?
  Bioinformatics, 22, 671-675.  
16879411 L.E.Dietrich, A.Price-Whelan, A.Petersen, M.Whiteley, and D.K.Newman (2006).
The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa.
  Mol Microbiol, 61, 1308-1321.  
16484493 T.Urich, C.M.Gomes, A.Kletzin, and C.Frazão (2006).
X-ray Structure of a self-compartmentalizing sulfur cycle metalloenzyme.
  Science, 311, 996.
PDB code: 2cb2
16049913 D.A.Sanders, J.R.Walker, T.Skarina, and A.Savchenko (2005).
The X-ray crystal structure of PA3566 from Pseudomonas aureginosa at 1.8 A resolution.
  Proteins, 61, 209-212.
PDB code: 1x7v
15686549 E.Déziel, S.Gopalan, A.P.Tampakaki, F.Lépine, K.E.Padfield, M.Saucier, G.Xiao, and L.G.Rahme (2005).
The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl-L-homoserine lactones.
  Mol Microbiol, 55, 998.  
15613473 M.A.Adams, and Z.Jia (2005).
Structural and biochemical evidence for an enzymatic quinone redox cycle in Escherichia coli: identification of a novel quinol monooxygenase.
  J Biol Chem, 280, 8358-8363.
PDB codes: 1r6y 1tuv
15779043 M.A.Willis, F.Song, Z.Zhuang, W.Krajewski, V.R.Chalamasetty, P.Reddy, A.Howard, D.Dunaway-Mariano, and O.Herzberg (2005).
Structure of YciI from Haemophilus influenzae (HI0828) reveals a ferredoxin-like alpha/beta-fold with a histidine/aspartate centered catalytic site.
  Proteins, 59, 648-652.
PDB code: 1mwq
16496224 M.J.Lemieux, C.Ference, M.M.Cherney, M.Wang, C.Garen, and M.N.James (2005).
The crystal structure of Rv0793, a hypothetical monooxygenase from M. tuberculosis.
  J Struct Funct Genomics, 6, 245-257.
PDB code: 1y0h
15845502 M.Palma, J.Zurita, J.A.Ferreras, S.Worgall, D.H.Larone, L.Shi, F.Campagne, and L.E.Quadri (2005).
Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR-dependent regulation of the bacterial oxidative stress adaptive response.
  Infect Immun, 73, 2958-2966.  
16260765 M.Revington, A.Semesi, A.Yee, and G.S.Shaw (2005).
Solution structure of the Escherichia coli protein ydhR: a putative mono-oxygenase.
  Protein Sci, 14, 3115-3120.
PDB code: 2asy
15701630 N.Funa, M.Funabashi, E.Yoshimura, and S.Horinouchi (2005).
A novel quinone-forming monooxygenase family involved in modification of aromatic polyketides.
  J Biol Chem, 280, 14514-14523.  
15520015 R.Wu, E.P.Skaar, R.Zhang, G.Joachimiak, P.Gornicki, O.Schneewind, and A.Joachimiak (2005).
Staphylococcus aureus IsdG and IsdI, heme-degrading enzymes with structural similarity to monooxygenases.
  J Biol Chem, 280, 2840-2846.
PDB codes: 1sqe 1xbw
15817470 Y.H.Chen, C.C.Wang, L.Greenwell, U.Rix, D.Hoffmeister, L.C.Vining, J.Rohr, and K.Q.Yang (2005).
Functional analyses of oxygenases in jadomycin biosynthesis and identification of JadH as a bifunctional oxygenase/dehydrase.
  J Biol Chem, 280, 22508-22514.  
15286722 A.T.Keatinge-Clay, D.A.Maltby, K.F.Medzihradszky, C.Khosla, and R.M.Stroud (2004).
An antibiotic factory caught in action.
  Nat Struct Mol Biol, 11, 888-893.
PDB code: 1tqy
15123249 B.Ostash, U.Rix, L.L.Rix, T.Liu, F.Lombo, A.Luzhetskyy, O.Gromyko, C.Wang, A.F.Braña, C.Méndez, J.A.Salas, V.Fedorenko, and J.Rohr (2004).
Generation of new landomycins by combinatorial biosynthetic manipulation of the LndGT4 gene of the landomycin E cluster in S. globisporus.
  Chem Biol, 11, 547-555.  
15326607 C.A.Bingman, K.A.Johnson, F.C.Peterson, R.O.Frederick, Q.Zhao, S.Thao, B.G.Fox, B.F.Volkman, W.B.Jeon, D.W.Smith, C.S.Newman, E.L.Ulrich, A.Hegeman, M.R.Sussman, J.L.Markley, and G.N.Phillips (2004).
Crystal structure of the protein from gene At3g17210 of Arabidopsis thaliana.
  Proteins, 57, 218-220.
PDB code: 1q4r
14570922 E.P.Skaar, A.H.Gaspar, and O.Schneewind (2004).
IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus.
  J Biol Chem, 279, 436-443.  
15297451 J.Valton, L.Filisetti, M.Fontecave, and V.Nivière (2004).
A two-component flavin-dependent monooxygenase involved in actinorhodin biosynthesis in Streptomyces coelicolor.
  J Biol Chem, 279, 44362-44369.  
15371455 O.Dgany, A.Gonzalez, O.Sofer, W.Wang, G.Zolotnitsky, A.Wolf, Y.Shoham, A.Altman, S.G.Wolf, O.Shoseyov, and O.Almog (2004).
The structural basis of the thermostability of SP1, a novel plant (Populus tremula) boiling stable protein.
  J Biol Chem, 279, 51516-51523.
PDB codes: 1si9 1tr0
15148379 O.T.Magnusson, H.Toyama, M.Saeki, A.Rojas, J.C.Reed, R.C.Liddington, J.P.Klinman, and R.Schwarzenbacher (2004).
Quinone biogenesis: Structure and mechanism of PqqC, the final catalyst in the production of pyrroloquinoline quinone.
  Proc Natl Acad Sci U S A, 101, 7913-7918.
PDB codes: 1otv 1otw
15231835 T.B.Thompson, K.Katayama, K.Watanabe, C.R.Hutchinson, and I.Rayment (2004).
Structural and functional analysis of tetracenomycin F2 cyclase from Streptomyces glaucescens. A type II polyketide cyclase.
  J Biol Chem, 279, 37956-37963.
PDB code: 1tuw
15103643 T.Wada, M.Shirouzu, T.Terada, Y.Kamewari, S.Y.Park, J.R.Tame, S.Kuramitsu, and S.Yokoyama (2004).
Crystal structure of the conserved hypothetical protein TT1380 from Thermus thermophilus HB8.
  Proteins, 55, 778-780.
PDB code: 1iuj
12878604 A.Jansson, J.Niemi, P.Mäntsälä, and G.Schneider (2003).
Crystal structure of aclacinomycin methylesterase with bound product analogues: implications for anthracycline recognition and mechanism.
  J Biol Chem, 278, 39006-39013.
PDB codes: 1q0r 1q0z
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.