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Cited by 279

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Crystal structure of DhbE, an archetype for aryl acid activating domains of modular nonribosomal peptide synthetases

Open access
May, Jürgen J., Kessler, Nadine, Marahiel, Mohamed A., Stubbs, Milton T.·2002·Proceedings of the National Academy of Sciences

Abstract

The synthesis of the catecholic siderophore bacillibactin is accomplished by the nonribosomal peptide synthetase (NRPS) encoded by the dhb operon. DhbE is responsible for the initial step in bacillibactin synthesis, the activation of the aryl acid 2,3-dihydroxybenzoate (DHB). The stand-alone adenylation (A) domain DhbE, the structure of which is presented here, exhibits greatest homology to other NRPS A-domains, acyl-CoA ligases and luciferases. It's structure is solved in three different states, without the ligands ATP and DHB (native state), with the product DHB-AMP (adenylate state) and with the hydrolyzed product AMP and DHB (hydrolyzed state). The 59.9-kDa protein folds into two domains, with the active site at the interface between them. In contrast to previous proposals of a major reorientation of the large and small domains on substrate binding, we observe only local structural rearrangements. The structure of the phosphate binding loop could be determined, a motif common to many adenylate-forming enzymes, as well as with bound DHB-adenylate and the hydrolyzed product DHB*AMP. Based on the structure and amino acid sequence alignments, an adapted specificity conferring code for aryl acid activating domains is proposed, allowing assignment of substrate specificity to gene products of previously unknown function.

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Metadata

Authors
May, J. J., Kessler, N., Marahiel, M. A., & Stubbs, M. T.
Venue
Proceedings of the National Academy of Sciences
Published
2002-09-09
Volume
99
Issue
19
Pages
12120-12125
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2016761967
Cited by
279
References
23
FWCI
6.52
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Crystal structure of DhbE, an archetype for aryl acid activating domains of modular nonribosomal peptide synthetases. https://app.cochat.ai/papers/10.1073/pnas.182156699
The paper
May, J. J., Kessler, N., Marahiel, M. A., & Stubbs, M. T. (2002). Crystal structure of DhbE, an archetype for aryl acid activating domains of modular nonribosomal peptide synthetases. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.182156699

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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