BotH
Comment
The bottromycin epimerase BotH defines a group of atypical alpha/beta-hydrolase-fold enzymes. BotH is a peptide epimerase responsible for the post-translational epimerization of L-Asp to D-Asp during bottromycin biosynthesis. D-amino acids endow peptides with diverse, desirable properties, but the post-translational and site-specific epimerization of L-amino acids into their D-counterparts is rare and chemically challenging. The activity does not rely on a catalytic triad. No conservation of Ser (replaced by Phe) nor His or Asp. The residues Phe110 and Val41 seem important in hydrogen bonding to substrate
Database
Interpro : No interpro
PIRSF : No PIRSF
Pdoc : No Pdoc
Pfam : No Pfam
Prints : No Print
EC Number : No EC Number
Sequences
| Peptide in | Fasta |
| Nucleotide in | Fasta |
| Alignment with Multalin | Text only |
| Seed alignment with MAFFT | No colour / coloured with Mview |
| Alignment with MAFFT | No colour / coloured with Mview |
| Dendrogram | The dnd file |
| Structure | Name | Proteins |
|---|---|---|
| 6T6H | Crystal structure of bottromycin epimerase BotH | 9actn-k4mhv9 |
| 6T6X | Structure of the Bottromycin epimerase BotH in complex with substrate | 9actn-k4mhv9 |
| 6T6Y | Structure of the Bottromycin epimerase BotH in complex with Bottromycin A2 | 9actn-k4mhv9 |
| 6T6Z | Structure of the Bottromycin epimerase BotH in complex with Bottromycin-A2 derivative | 9actn-k4mhv9 |
| 6T70 | Structure of the Bottromycin epimerase BotH in complex with Bottromycin A2 derivative | 9actn-k4mhv9 |
| Gene_locus | Name | Species |
|---|---|---|
| 9actn-P028797636 | Streptomyces purpureus alpha\/beta fold hydrolase | Streptomyces purpureus |
| 9actn-P161684282 | Micromonospora sp. NEAU-HG-1 alpha\/beta fold hydrolase | Micromonospora sp. NEAU-HG-1 |
| 9actn-k0p1p9 | Streptomyces bottropensis. BmbG protein | Streptomyces bottropensis ATCC 25435 |
| 9actn-k4jvv8 | Streptomyces sp. WMMB 272. Alpha-beta hydrolase | Streptomyces sp. WMMB 272 |
| 9actn-k4mhv9 |  Streptomyces sp. BC16019 BotH bottromycin epimerase |
Streptomyces sp. BC16019 |
| 9actn-l1l6k1 | Streptomyces ipomoeae 91-03. AB hydrolase-1 domain-containing protein | Streptomyces ipomoeae 91-03 |
| salto-P080676991 | Salinispora tropica alpha\/beta fold hydrolase | Salinispora tropica |
| stron-P109280139 | Streptomyces orinoci alpha\/beta fold hydrolase | Streptomyces orinoci |
| strsc-a0a117ee86 | Streptomyces scabiei. Short chain dehydrogenase | Streptomyces scabiei |
| strsw-c9z180 | Streptomyces scabiei (strain 87.22). AB hydrolase-1 domain-containing protein | Streptomyces scabiei |
| Substrate | Chemical Nomenclature | Proteins |
|---|---|---|
| Bottromycin-A2 | methyl 3-[[2-[[2-[(6-tert-butyl-13-methyl-2,8,11-trioxo-9-propan-2-yl-1,4,7,10-tetrazabicyclo[10.3.0]pentadec-4-en-5-yl)amino]-3,3-dimethylbutanoyl]amino]-3-phenylbutanoyl]amino]-3-(1,3-thiazol-2-yl)propanoate | 9actn-k4mhv9 |
| Bottromycin-A2-MKW | (4R)-2-[(1R)-2-Carboxy-1-[[(2S)-2-[[(2S)-3-methyl-2-[[(6S,9S,12S)-2,8,11-trioxo-6,9-di(propan-2-yl)-1,4,7,10-tetrazabicyclo[10.3.0]pentadec-4-en-5-yl]amino]butanoyl]amino]-3-phenylpropanoyl]amino]ethyl]-4,5-dihydro-1,3-thiazole-4-carboxylic acid | 9actn-k4mhv9 |
| Bottromycin-A2-derivative-MQZ | methyl (3~{R})-3-[[(2~{S},3~{S})-2-[[(2~{S})-2-[(~{E})-[(6~{S},9~{S},12~{S},13~{R})-6-~{tert}-butyl-13-methyl-9-(2-methylsulfinylethyl)-2,8,11-tris(oxidanylidene)-1,4,7,10-tetrazabicyclo[10.3.0]pentadecan-5-ylidene]amino]-3,3-dimethyl-butanoyl]amino]-3-phenyl-butanoyl]amino]-3-(1,3-thiazol-2-yl)propanoate | 9actn-k4mhv9 |
| Bottromycin-A2-derivative-MRB | methyl (3R)-3-[[(2S,3S)-2-[[(2S)-2-[[(6S,9S,12S,13R)-6-tert-butyl-13-methyl-9-(2-methylsulfanylethyl)-2,8,11-trioxo-1,4,7,10-tetrazabicyclo[10.3.0]pentadec-4-en-5-yl]amino]-3,3-dimethylbutanoyl]amino]-3-phenylbutanoyl]amino]-3-(1,3-thiazol-2-yl)propanoate | 9actn-k4mhv9 |
References (1)
| Title : The bottromycin epimerase BotH defines a group of atypical alpha\/beta-hydrolase-fold enzymes - Sikandar_2020_Nat.Chem.Biol_16_1013 |
| Author(s) : Sikandar A , Franz L , Adam S , Santos-Aberturas J , Horbal L , Luzhetskyy A , Truman AW , Kalinina OV , Koehnke J |
| Ref : Nat Chemical Biology , 16 :1013 , 2020 |
| Abstract : |
| PubMedSearch : Sikandar_2020_Nat.Chem.Biol_16_1013 |
| PubMedID: 32601484 |
| Gene_locus related to this paper: 9actn-k4mhv9 |