2ar8

From Proteopedia

(Difference between revisions)

Revision as of 08:36, 27 January 2021

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

Structural highlights

2ar8 is a 1 chain structure with sequence from "bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2apg, 2aqj
Gene:	PrnA ("Bacillus fluorescens liquefaciens" Flugge 1886)
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.

Publication Abstract from PubMed

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.

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:16195462^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Dong C, Flecks S, Unversucht S, Haupt C, van Pee KH, Naismith JH. Tryptophan 7-halogenase (PrnA) structure suggests a mechanism for regioselective chlorination. Science. 2005 Sep 30;309(5744):2216-9. PMID:16195462 doi:309/5744/2216

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ar8"

@@ Line 1: / Line 1: @@
 ==The structure of tryptophan 7-halogenase (PrnA)suggests a mechanism for regioselective chlorination==
-<StructureSection load='2ar8' size='340' side='right' caption='[[2ar8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='2ar8' size='340' side='right'caption='[[2ar8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ar8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AR8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ar8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AR8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CTE:7-CHLOROTRYPTOPHAN'>CTE</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
+</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=CTE:7-CHLOROTRYPTOPHAN'>CTE</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2apg|2apg]], [[2aqj|2aqj]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2apg|2apg]], [[2aqj|2aqj]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PrnA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PrnA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ar8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ar8 OCA], [http://pdbe.org/2ar8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ar8 RCSB], [http://www.ebi.ac.uk/pdbsum/2ar8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ar8 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ar8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ar8 OCA], [https://pdbe.org/2ar8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ar8 RCSB], [https://www.ebi.ac.uk/pdbsum/2ar8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ar8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[[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]]
@@ Line 35: / Line 35: @@
 </StructureSection>
 [[Category: Bacillus fluorescens liquefaciens flugge 1886]]
+[[Category: Large Structures]]
 [[Category: Dong, C]]
 [[Category: Flecks, S]]

2ar8

From Proteopedia

Revision as of 08:36, 27 January 2021

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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