Linear gramicidin synthase

Function

Linear gramicidin synthase LgrA is a biosynthetic enzyme which synthesizes natural products for therapeutics using a modular synthetic logic where each module adds one amino acid to the growing chain.

Thus, LgrA is a non-ribosomal peptide synthetase^[1]. Linear gramicidin is a 15 amino acid long polypeptide which is synthetized by synthases LgrA, LgrB, LgrC, LgrD which comprise 16 modules^[2].

Structural highlights

LgrA core contains 3 essential domains. Adenylation domain which activates the specific amino acid by adenylation, the thiolation domain which produces a thiol ester and the condensation domain which catalyzes the elongation of the peptide chain^[3].

Linear gramicidin synthease subunit A initiation module complex with sulfate (PDB code 5es5).

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Updated on 05-October-2020

3D structures of linear gramicidin synthase subunit A3D structures of linear gramicidin synthase subunit A

5jnf, 5es6 - BpLgrA 2 domains 2-584 - Brevibacillus parabrevis
6ulz - BpLgrA adenylation domain (mutant) 2-684
5es7 - BpLgrA adenylation domain 2-684 + Val + APC + FON
5es5, 5es8, 5es9 - BpLgrA initiation domain 2-766
6mfw - BpLgrA 4 domains 2-1198
6mfx - BpLgrA 4 domains (mutant) 2-1198
6mfy, 6mg0 - BpLgrA 5 domains 2-1716
6mfz - BpLgrA 2-1802

ReferencesReferences

↑ Reimer JM, Eivaskhani M, Harb I, Guarne A, Weigt M, Schmeing TM. Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility. Science. 2019 Nov 8;366(6466). pii: 366/6466/eaaw4388. doi:, 10.1126/science.aaw4388. PMID:31699907 doi:http://dx.doi.org/10.1126/science.aaw4388
↑ Schracke N, Linne U, Mahlert C, Marahiel MA. Synthesis of linear gramicidin requires the cooperation of two independent reductases. Biochemistry. 2005 Jun 14;44(23):8507-13. PMID:15938641 doi:http://dx.doi.org/10.1021/bi050074t
↑ Reimer JM, Aloise MN, Harrison PM, Schmeing TM. Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase. Nature. 2016 Jan 14;529(7585):239-42. doi: 10.1038/nature16503. PMID:26762462 doi:http://dx.doi.org/10.1038/nature16503

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Michal Harel

[1] Reimer JM, Eivaskhani M, Harb I, Guarne A, Weigt M, Schmeing TM. Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility. Science. 2019 Nov 8;366(6466). pii: 366/6466/eaaw4388. doi:, 10.1126/science.aaw4388. PMID:31699907 doi:http://dx.doi.org/10.1126/science.aaw4388

[2] Schracke N, Linne U, Mahlert C, Marahiel MA. Synthesis of linear gramicidin requires the cooperation of two independent reductases. Biochemistry. 2005 Jun 14;44(23):8507-13. PMID:15938641 doi:http://dx.doi.org/10.1021/bi050074t

[3] Reimer JM, Aloise MN, Harrison PM, Schmeing TM. Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase. Nature. 2016 Jan 14;529(7585):239-42. doi: 10.1038/nature16503. PMID:26762462 doi:http://dx.doi.org/10.1038/nature16503

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