Structural highlights
Function
BACC_BACSU Part of the bacABCDEFG operon responsible for the biosynthesis of bacilysin, an irreversible inactivator of the glutaminase domain of glucosamine synthetase. Catalyzes the dehydrogenation of the C7-hydroxyl group in the 4S-tetrahydrotyrosine (4S-H4Tyr) to yield anticapsin (epoxycyclohexanonyl-Ala). It is not able to oxidize the 4R-H4Tyr diastereomer and the dihydrobacilysin dipeptide (L-Ala-4S-H4Tyr dipeptide).[1] [2]
Publication Abstract from PubMed
Bacillus subtilis BacC is an oxidoreductase involved in the biosynthesis of the potent antibiotic bacilysin. The crystal structure of BacC was determined at 1.19 A resolution. An experimental charge density approach was used to calculate non-covalent interactions within the monomer and across the dimeric interface of BacC. This interaction network, in turn, enabled an analysis of non-covalently connected paths that span the protein structure. One of the pathways of non-covalent interactions was examined by mutational analysis. Biochemical analysis of BacC mutants with potential disruptions in non-covalent interactions along this path revealed that residues that form nodes in pathways of non-covalent interactions influence catalytic activity more than others in a similar chemical environment. Furthermore, we note that nodes in the non-covalent interaction networks are co-localized with compensatory mutation sites identified by multiple sequence alignment of proteins with low sequence similarity to BacC. Put together, this analysis supports the hypothesis that non-covalent nodes represent conserved structural features that can impact the catalytic activity of an enzyme.
Probing the influence of non-covalent contact networks identified by charge density analysis on the oxidoreductase BacC.,Perinbam K, Balaram H, Guru Row TN, Gopal B Protein Eng Des Sel. 2017 Mar 1;30(3):265-272. doi: 10.1093/protein/gzx006. PMID:28158843[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Steinborn G, Hajirezaei MR, Hofemeister J. bac genes for recombinant bacilysin and anticapsin production in Bacillus host strains. Arch Microbiol. 2005 Feb;183(2):71-9. Epub 2004 Dec 18. PMID:15609023 doi:http://dx.doi.org/10.1007/s00203-004-0743-8
- ↑ Parker JB, Walsh CT. Action and timing of BacC and BacD in the late stages of biosynthesis of the dipeptide antibiotic bacilysin. Biochemistry. 2013 Feb 5;52(5):889-901. doi: 10.1021/bi3016229. Epub 2013 Jan 23. PMID:23317005 doi:http://dx.doi.org/10.1021/bi3016229
- ↑ Perinbam K, Balaram H, Guru Row TN, Gopal B. Probing the influence of non-covalent contact networks identified by charge density analysis on the oxidoreductase BacC. Protein Eng Des Sel. 2017 Mar 1;30(3):265-272. doi: 10.1093/protein/gzx006. PMID:28158843 doi:http://dx.doi.org/10.1093/protein/gzx006
