The Second Enzyme in Pyrrolnitrin Biosynthetic Pathway Is Related to the Heme-Dependent Dioxygenase Superfamily,

Laurentis, Walter De; Leang, Khim; Anderson, J. L. Ross; Adam, Ariane; Johnson, Kenneth A.; Phillips, Robert S.; Chapman, Stephen K; Pée, Karl‐Heinz van; Naismith, James H.

doi:10.1021/bi702167m

Cited by 7 publications

(12 citation statements)

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“…21 On the other hand, MCM are well-known tools for the analysis of biological sequence data. Here, we give for the first time a simple but general MCM to calculate average potentials and compare them with enzyme/nonenzyme discrimination QSAR studies.…”

Section: Lda-qsar Modelsmentioning

confidence: 99%

Computational chemistry study of 3D‐structure‐function relationships for enzymes based on Markov models for protein electrostatic, HINT, and van der Waals potentials

et al. 2008

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In a significant work, Dobson and Doig (J Mol Biol 2003, 330, 771) illustrated protein prediction as enzymatic or not from spatial structure without resorting to alignments. They used 52 protein features and a nonlinear support vector machine model to classify more than 1000 proteins collected from the PDB with a 77% overall accuracy. The most useful features were: the secondary-structure content, the amino acid frequencies, the number of disulphide bonds, and the largest cleft size. Working on the same dataset used by D&D, in this article we reported a good and simple model, based on the Markov chain models (MCM), to classify protein 3D structures as enzymatic or not, taking into consideration the spatial structure without resorting to alignments. Here we define, for the first time, a general MCM to calculate the electrostatic potential, molecular vibrations, van der Waals (vdw) interactions, and hydrophobic interactions (HINT) and use them in comparative studies of potential fields and/or protein function prediction. The dataset is composed of 1371 proteins divided into 689 enzymes and 682 nonenzymes, all proteins were collected from the PDB. The best model we found was a linear model carried out with the linear discriminant analysis; it was able to classify 74.18% of the proteins using only two electrostatic potentials. In the work described here, we define 3D-HINT potentials (mu(k)) and use them for the first time to derive a classifier for protein enzymes. We analyzed ROC curves, domain of applicability, parametric assumptions, desirability maps, and also tested other nonlinear artificial neural network models which did not improve the linear model. In closing, this MCM allows a fast calculation and comparison of different potentials deriving into accurate protein 3D structure-function relationships, notably simpler than the previous.

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Section: Lda-qsar Modelsmentioning

confidence: 99%

Computational chemistry study of 3D‐structure‐function relationships for enzymes based on Markov models for protein electrostatic, HINT, and van der Waals potentials

et al. 2008

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“…Interestingly, the L-tryptophan complexes of the two proteins are quite similar, with the indole nitrogen pointing down towards the haem [13] ( Figure 2B). The other three PrnB substrate complexes differ from the L-tryptophan complex and have the indole ring nitrogen pointing away from the haem [13] ( Figure 3B).…”

Section: Prnb An Unexpected Addition To the Familymentioning

confidence: 95%

“…PrnB is thought to catalyse an entirely different reaction when compared with the TDO/IDO superfamily enzymes, with an indole rearrangement of 7-chlorotryptophan [13] ( Figure 3A), which occurs in the pyrrolnitrin pathway [14]. The structure of PrnB from Pseudomonas revealed it to be a very close homologue of TDO and IDO.…”

Section: Prnb An Unexpected Addition To the Familymentioning

confidence: 99%

“…The structure of PrnB from Pseudomonas revealed it to be a very close homologue of TDO and IDO. There were some differences between the active sites, most significantly a loop in PrnB which partly shields the haem from the incoming substrate, as well as a slightly different arrangement of residues above the haem [13]. The fact that PrnB was related to IDO was very interesting, since the overall reaction that it is thought to catalyse does not result in the insertion of oxygen.…”

Section: Prnb An Unexpected Addition To the Familymentioning

confidence: 99%

“…The fact that PrnB was related to IDO was very interesting, since the overall reaction that it is thought to catalyse does not result in the insertion of oxygen. A mechanism involving the insertion and removal of oxygen during turnover was suggested on the basis of the multiple (D-and L-tryptophan, and 7-chloro-D-and 7-chloro-L-tryptophan) co-complex structures [13]. As a warning of the dangers of interpreting binary complexes, the L-tryptophan was bound differently from the other three substrate mimics, and, in all co-complex structures, the iron was ligated by either the amino or carboxy group of the substrate.…”

Section: Prnb An Unexpected Addition To the Familymentioning

confidence: 99%

See 2 more Smart Citations

Tryptophan oxygenation: mechanistic considerations

Naismith

2012

Biochemical Society Transactions

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From a protein structural viewpoint, tryptophan is often considered an inert structural amino acid, playing a role as a hydrophobic anchor in membrane proteins or as part of the hydrophobic core of soluble proteins. However, tryptophan is the only polyaromatic amino acid and, from a chemical viewpoint, possesses unique reactivity owing to the electron-richness of the indole system. This reactivity is seen in the area of natural products and metabolites which have exquisite modifications of the indole ring system. Enzymes have evolved multiple strategies to break or modify the indole ring; one particular class is the IDO/TDO (indoleamine/tryptophan dioxygenase) superfamily. A new member of this family, PrnB, on the surface catalyses a very different reaction, but actually shares much of the early chemistry with the tryptophan dioxygenases. Studies on PrnB have contributed to our understanding of the wider superfamily. In the present mini-review, recent developments in our understanding of how the TDO class of enzymes use activated molecular oxygen to break the indole ring are discussed.

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Treatment of reoccurring instent restenosis following reintervention after stent‐supported renal artery angioplasty

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Rastan

et al. 2007

Cathet Cardio Intervent

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The Second Enzyme in Pyrrolnitrin Biosynthetic Pathway Is Related to the Heme-Dependent Dioxygenase Superfamily,

Cited by 7 publications

References 0 publications

Computational chemistry study of 3D‐structure‐function relationships for enzymes based on Markov models for protein electrostatic, HINT, and van der Waals potentials

Computational chemistry study of 3D‐structure‐function relationships for enzymes based on Markov models for protein electrostatic, HINT, and van der Waals potentials

Tryptophan oxygenation: mechanistic considerations

Treatment of reoccurring instent restenosis following reintervention after stent‐supported renal artery angioplasty

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