| Structural highlights
2x68 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: | 2v7i, 2v7k, 2x66, 2v7m, 2v7l, 2v7j, 2x67 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[PRNB_PSEFL] Involved in the biosynthesis of the antifungal antibiotic pyrrolnitrin. Catalyzes the ring rearrangement and decarboxylation to convert 7-chloro-L-tryptophan (7-CLT) to monodechloroaminopyrrolnitrin (MDA). It can also use 7-chloro-D-tryptophan, but 7-chloro-L-tryptophan is the preferred natural enantiomer.[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
Pyrrolnitrin (3-chloro-4-(2'-nitro-3'-chlorophenyl)pyrrole) is a broad-spectrum antifungal compound isolated from Pseudomonas pyrrocinia. Four enzymes (PrnA, PrnB, PrnC, and PrnD) are required for pyrrolnitrin biosynthesis from tryptophan. PrnB rearranges the indole ring of 7-Cl-l-tryptophan and eliminates the carboxylate group. PrnB shows robust activity in vivo, but in vitro activity for PrnB under defined conditions remains undetected. The structure of PrnB establishes that the enzyme belongs to the heme b-dependent indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) family. We report the cyanide complex of PrnB and two ternary complexes with both l-tryptophan or 7-Cl-l-tryptophan and cyanide. The latter two complexes are essentially identical and mimic the likely catalytic ternary complex that occurs during turnover. In the cyanide ternary complexes, a loop previously disordered becomes ordered, contributing to the binding of substrates. The conformations of the bound tryptophan substrates are changed from that seen previously in the binary complexes. In l-tryptophan ternary complex, the indole ring now adopts the same orientation as seen in the PrnB binary complexes with other tryptophan substrates. The amide and carboxylate group of the substrate are orientated in a new conformation. Tyr(321) and Ser(332) play a key role in binding these groups. The structures suggest that catalysis requires an l-configured substrate. Isothermal titration calorimetry data suggest d-tryptophan does not bind after cyanide (or oxygen) coordinates with the distal (or sixth) site of heme. This is the first ternary complex with a tryptophan substrate of a member of the tryptophan dioxygenase superfamily and has mechanistic implications.
The ternary complex of PrnB (the second enzyme in the pyrrolnitrin biosynthesis pathway), tryptophan, and cyanide yields new mechanistic insights into the indolamine dioxygenase superfamily.,Zhu X, van Pee KH, Naismith JH J Biol Chem. 2010 Jul 2;285(27):21126-33. Epub 2010 Apr 26. PMID:20421301[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ De Laurentis W, Khim L, Anderson JL, Adam A, Johnson KA, Phillips RS, Chapman SK, van Pee KH, Naismith JH. The second enzyme in pyrrolnitrin biosynthetic pathway is related to the heme-dependent dioxygenase superfamily. Biochemistry. 2007 Oct 30;46(43):12393-404. Epub 2007 Oct 9. PMID:17924666 doi:10.1021/bi7012189
- ↑ 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
- ↑ Zhu X, van Pee KH, Naismith JH. The ternary complex of PrnB (the second enzyme in the pyrrolnitrin biosynthesis pathway), tryptophan, and cyanide yields new mechanistic insights into the indolamine dioxygenase superfamily. J Biol Chem. 2010 Jul 2;285(27):21126-33. Epub 2010 Apr 26. PMID:20421301 doi:10.1074/jbc.M110.120485
|
