2aqj: Difference between revisions

Latest revision as of 09:13, 14 February 2024

The structure of tryptophan 7-halogenase (PrnA) suggests a mechanism for regioselective chlorination

Structural highlights

2aqj is a 1 chain structure with sequence from Pseudomonas fluorescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	CL, FAD, TRP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PRNA_PSEFL Involved in the biosynthesis of the antifungal antibiotic pyrrolnitrin. Catalyze the chlorination of tryptophan (Trp) at C7 position to yield 7-chloro-L-tryptophan (7-CLT). The reaction between FADH2, Cl-, and O2 generates the powerful oxidant HOCl, which is presumed to carry out the chlorination reaction. The reaction of HOCl with the active site Lys-79 generates a lysine chloramine, which plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes. It is also able to use bromide ions to generate monobrominated Trp.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Keller S, Wage T, Hohaus K, Holzer M, Eichhorn E, van Pee KH. Purification and Partial Characterization of Tryptophan 7-Halogenase (PrnA) from Pseudomonas fluorescens This work was supported by the Deutsche Forschungsgemeinschaft (DFG) through the Graduiertenkolleg "Struktur-Eigenschafts-Beziehungen bei Heterocyclen", the Environment and Climate Research and Technology Development Programme of the European Union, the Sachsische Staatsministerium fur Umwelt und Landesentwicklung, the Max-Buchner-Stiftung, and the Fonds der Chemischen Industrie. Samples of P. fluorescens BL915DeltaORF1-4 with pPEH14(prnA) and pPEH14(prnC) were obtained from Dr. J. M. Ligon, Novartis Agribusiness Biotechnology Research, Inc., Research Triangle, NC (USA) and NADH oxidase (from Thermus thermiphilus) from Prof. Helmut Erdmann, Fachhochschule Flensburg (Germany). Angew Chem Int Ed Engl. 2000 Jul 3;39(13):2300-2302. PMID:10941070
↑ Hammer PE, Hill DS, Lam ST, Van Pee KH, Ligon JM. Four genes from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin. Appl Environ Microbiol. 1997 Jun;63(6):2147-54. PMID:9172332
↑ Kirner S, Hammer PE, Hill DS, Altmann A, Fischer I, Weislo LJ, Lanahan M, van Pee KH, Ligon JM. Functions encoded by pyrrolnitrin biosynthetic genes from Pseudomonas fluorescens. J Bacteriol. 1998 Apr;180(7):1939-43. PMID:9537395

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Keller S, Wage T, Hohaus K, Holzer M, Eichhorn E, van Pee KH. Purification and Partial Characterization of Tryptophan 7-Halogenase (PrnA) from Pseudomonas fluorescens This work was supported by the Deutsche Forschungsgemeinschaft (DFG) through the Graduiertenkolleg "Struktur-Eigenschafts-Beziehungen bei Heterocyclen", the Environment and Climate Research and Technology Development Programme of the European Union, the Sachsische Staatsministerium fur Umwelt und Landesentwicklung, the Max-Buchner-Stiftung, and the Fonds der Chemischen Industrie. Samples of P. fluorescens BL915DeltaORF1-4 with pPEH14(prnA) and pPEH14(prnC) were obtained from Dr. J. M. Ligon, Novartis Agribusiness Biotechnology Research, Inc., Research Triangle, NC (USA) and NADH oxidase (from Thermus thermiphilus) from Prof. Helmut Erdmann, Fachhochschule Flensburg (Germany). Angew Chem Int Ed Engl. 2000 Jul 3;39(13):2300-2302. PMID:10941070

[2] Hammer PE, Hill DS, Lam ST, Van Pee KH, Ligon JM. Four genes from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin. Appl Environ Microbiol. 1997 Jun;63(6):2147-54. PMID:9172332

[3] Kirner S, Hammer PE, Hill DS, Altmann A, Fischer I, Weislo LJ, Lanahan M, van Pee KH, Ligon JM. Functions encoded by pyrrolnitrin biosynthetic genes from Pseudomonas fluorescens. J Bacteriol. 1998 Apr;180(7):1939-43. PMID:9537395

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-[[Image:2aqj.gif|left|200px]]<br /><applet load="2aqj" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2aqj, resolution 1.800&Aring;" />
-'''The structure of tryptophan 7-halogenase (PrnA) suggests a mechanism for regioselective chlorination'''<br />
-==Overview==
+==The structure of tryptophan 7-halogenase (PrnA) suggests a mechanism for regioselective chlorination==
-Chlorinated natural products include vancomycin and cryptophycin A. Their, biosynthesis involves regioselective chlorination by flavin-dependent, halogenases. We report the structural characterization of tryptophan, 7-halogenase (PrnA), which regioselectively chlorinates tryptophan., Tryptophan and flavin adenine dinucleotide (FAD) are separated by a 10, angstrom-long tunnel and bound by distinct enzyme modules. The FAD module, is conserved in halogenases and is related to flavin-dependent, monooxygenases. On the basis of biochemical studies, crystal structures, and by analogy with monooxygenases, we predict that FADH2 reacts with O2, to make peroxyflavin, which is decomposed by Cl-. The resulting HOCl is, guided through the tunnel to tryptophan, where it is activated to, participate in electrophilic aromatic substitution.
+<StructureSection load='2aqj' size='340' side='right'caption='[[2aqj]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[2aqj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AQJ FirstGlance]. <br>
-AQJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=TRP:'>TRP</scene> and <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AQJ OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2aqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aqj OCA], [https://pdbe.org/2aqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aqj RCSB], [https://www.ebi.ac.uk/pdbsum/2aqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aqj ProSAT]</span></td></tr>
-Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination., Dong C, Flecks S, Unversucht S, Haupt C, van Pee KH, Naismith JH, Science. 2005 Sep 30;309(5744):2216-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16195462 16195462]
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PRNA_PSEFL PRNA_PSEFL] Involved in the biosynthesis of the antifungal antibiotic pyrrolnitrin. Catalyze the chlorination of tryptophan (Trp) at C7 position to yield 7-chloro-L-tryptophan (7-CLT). The reaction between FADH2, Cl-, and O2 generates the powerful oxidant HOCl, which is presumed to carry out the chlorination reaction. The reaction of HOCl with the active site Lys-79 generates a lysine chloramine, which plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes. It is also able to use bromide ions to generate monobrominated Trp.<ref>PMID:10941070</ref> <ref>PMID:9172332</ref> <ref>PMID:9537395</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aq/2aqj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2aqj ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Pseudomonas fluorescens]]
-[[Category: Single protein]]
+[[Category: Dong C]]
-[[Category: Dong, C.]]
+[[Category: Flecks S]]
-[[Category: Flecks, S.]]
+[[Category: Haupt C]]
-[[Category: Haupt, C.]]
+[[Category: Naismith JH]]
-[[Category: Naismith, J.H.]]
+[[Category: Unversucht S]]
-[[Category: Pee, K.H.Van.]]
+[[Category: Van Pee K-H]]
-[[Category: SSPF, Scottish.Structural.Proteomics.Facility.]]
-[[Category: Unversucht, S.]]
-[[Category: CL]]
-[[Category: FAD]]
-[[Category: TRP]]
-[[Category: flavin-dependent halogenase]]
-[[Category: helical bundle]]
-[[Category: sandwiched sheets]]
-[[Category: scottish structural proteomics facility]]
-[[Category: sspf]]
-[[Category: structural genomics]]
-[[Category: tryptophan 7-halogenase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 18:07:49 2008''

2aqj: Difference between revisions

Latest revision as of 09:13, 14 February 2024

The structure of tryptophan 7-halogenase (PrnA) suggests a mechanism for regioselective chlorination

Structural highlights

Function

Evolutionary Conservation

References

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