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4iz6

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Structure of EntE and EntB, an NRPS adenylation-PCP fusion protein with pseudo translational symmetry

Structural highlights

4iz6 is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENTB_ECOLI Required for production of 2,3-DHB. Also serves as an aryl carrier protein and plays a role in enterobactin assembly.ENTE_ECOLI Activates the carboxylate group of 2,3-dihydroxy-benzoate (2,3-DHB), via ATP-dependent PPi exchange reactions, to the acyladenylate. Then, catalyzes the acylation of holo-EntB with 2,3-DHB adenylate, preparing that molecule for amide bond formation with L-serine.

Publication Abstract from PubMed

The nonribosomal peptide synthetases (NRPSs) are a family of modular proteins that contain multiple catalytic domains joined in a single protein. Together, these domains work to produce chemically diverse peptides, including compounds with antibiotic activity or that play a role in iron acquisition. Understanding the structural mechanisms that govern the domain interactions has been a long-standing goal. During NRPS synthesis, amino-acid substrates are loaded onto integrated carrier protein domains through the activity of NRPS adenylation domains. The structures of two adenylation domain-carrier protein domain complexes have recently been determined in an effort that required the use of a mechanism-based inhibitor to trap the domain interaction. Here, the continued analysis of these proteins is presented, including a higher resolution structure of an engineered di-domain protein containing the EntE adenylation domain fused with the carrier protein domain of its partner EntB. The protein crystallized in a novel space group in which molecular replacement and refinement were challenged by noncrystallographic pseudo-translational symmetry. The structure determination and how the molecular packing impacted the diffraction intensities are reported. Importantly, the structure illustrates that in this new crystal form the functional interface between the adenylation domain and the carrier protein domain remains the same as that observed previously. At a resolution that allows inclusion of water molecules, additional interactions are observed between the two protein domains and between the protein and its ligands. In particular, a highly solvated region that surrounds the carrier protein cofactor is described.

Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry.,Sundlov JA, Gulick AM Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1482-92. doi:, 10.1107/S0907444913009372. Epub 2013 Jul 18. PMID:23897471^[1]

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

References

↑ Sundlov JA, Gulick AM. Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry. Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1482-92. doi:, 10.1107/S0907444913009372. Epub 2013 Jul 18. PMID:23897471 doi:http://dx.doi.org/10.1107/S0907444913009372