O-Acetylhomoserine Sulfhydrylase as a Key Enzyme of Direct Sulfhydrylation in Microbial Methionine Biosynthesis
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| 1. | Title | Title of document | O-Acetylhomoserine Sulfhydrylase as a Key Enzyme of Direct Sulfhydrylation in Microbial Methionine Biosynthesis |
| 2. | Creator | Author's name, affiliation, country | V. V. Kulikova; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 2. | Creator | Author's name, affiliation, country | E. A. Morozova; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 2. | Creator | Author's name, affiliation, country | A. D. Lyfenko; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 2. | Creator | Author's name, affiliation, country | V. S. Koval; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 2. | Creator | Author's name, affiliation, country | N. V. Anufrieva; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 2. | Creator | Author's name, affiliation, country | P. N. Solyev; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 2. | Creator | Author's name, affiliation, country | S. V. Revtovich; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Russian Federation |
| 3. | Subject | Discipline(s) | |
| 3. | Subject | Keyword(s) | O-Acetylhomoserine Sulfhydrylase; methionine biosynthesis; direct sulfhydrylation |
| 4. | Description | Abstract | Methionine biosynthesis in most microorganisms proceeds in two alternative ways. Each pathway is catalyzed by independent enzymes and is tightly regulated by methionine. The transulfurylation pathway involves the formation of a cystathionine, and cysteine acts as a source of sulfur. The enzymes of this metabolic pathway are characterized in detail. The direct sulfhydrylation pathway involves the synthesis of homocysteine with the participation of an inorganic sulfur source directly from O-acetylhomoserine and is predominant in most classes of bacteria. The subject of this review is the properties and functioning of one of the least studied enzymes of the direct sulfhydrylation pathway – O-acetylhomoserine sulfhydrylase. A deep understanding of the mechanisms controlling the substrate and reaction specificity of O-acetylhomoserine sulfhydrylase is a necessary step in the rational redesign of the enzyme in order to create a promising catalyst for the synthesis s of methionine and its derivatives, as well as, in combination with crystallographic data, for the development of new antimicrobial compounds based on effective enzyme inhibitors. |
| 5. | Publisher | Organizing agency, location | The Russian Academy of Sciences |
| 6. | Contributor | Sponsor(s) |
Russian Science Foundation (№ 22–24–00255) |
| 7. | Date | (DD-MM-YYYY) | 27.11.2024 |
| 8. | Type | Status & genre | Peer-reviewed Article |
| 8. | Type | Type | Research Article |
| 9. | Format | File format | |
| 10. | Identifier | Uniform Resource Identifier | https://rjonco.com/0555-1099/article/view/674549 |
| 10. | Identifier | Digital Object Identifier (DOI) | 10.31857/S0555109924030017 |
| 10. | Identifier | eLIBRARY Document Number (EDN) | EXEKTZ |
| 11. | Source | Title; vol., no. (year) | Prikladnaâ biohimiâ i mikrobiologiâ; Vol 60, No 3 (2024) |
| 12. | Language | English=en | ru |
| 13. | Relation | Supp. Files |
Fig. 1. Biosynthesis of methionine in microorganisms. (75KB) Fig. 2. Scheme of the γ-substitution reaction catalyzed by OAHS. (12KB) Fig. 3. Alignment of OAHS amino acid sequences from Campylobacter jejuni (Cje; 4OC9), Mycobacterium marinum (Mma; B2HDS7), T. maritima (Tma; Q9WZY4), T. thermophilus (Tth1; Q5SK88 and Tth2; Q5SJ58), W. succinogenes (Wsu; Q7M9C8), Clostridium novyi (Cno; A0A5B8NEI4), Clostridium difficile (Cdi; A0A1L7H895), L. meyeri (Lme; P94890), M. tuberculosis (Mtu; L7N4M1), Saccharomyces cerevisiae (Sce; P06106). Conserved residues are marked in black. Enzyme sequences with known 3D structures are marked with a vertical line; triangles mark the functional residues of the active center. (273KB) Fig. 4. Proposed mechanism of the OAHS-catalyzed γ-substitution reaction. (51KB) Fig. 5. Tetrameric organization of OAHS using the structure of the enzyme from T. thermophilus as an example (pdb code 2ctz). (74KB) Fig. 6. Superposition of polypeptide chains (a) of spatial structures of OASH from different microorganisms: C. jejuni OAHS (pdb code 4OC9) – dark blue, M. marinum OASH (pdb code 4KAM) – light blue, T. maritima OASH (pdb code 7KB1) – purple, T. thermophilus OASH (pdb code 2CTZ) – green, T. thermophilus OASH (pdb code 2CB1) – dark green, W. succinogenes OASH (pdb code 3RI6) – orange; (b) spatial structures of enzymes of the CBL subclass: T. maritima OASH (pdb code 7KB1) – orange, Citrobacter freundii methionine γ-lyase MGL (pdb code 2RFV) – dark blue, Arabidopsis thaliana CBL (pdb code 1IBJ) – light blue, Nicotiana tabacum CGS (pdb code 1I41) – green, S. cerevisiae cystathionine γ-lyase (pdb code 1N8P) – purple. The unique fragment characteristic of the OASH enzyme is highlighted in oval. (32KB) Fig. 7. Scheme of interactions of α,β-unsaturated ketimine with amino acid residues of the active center of OAHS (T. maritima numbering). Amino acid residues of the neighboring monomer are indicated by an asterisk. Dashed lines show hydrogen bonds, and dotted lines show π-interactions. (46KB) Fig. 8. Absorption spectra of OAHS from C. difficile (a) and C. novyi (b) at pH 7.5. (18KB) |
| 14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
| 15. | Rights | Copyright and permissions |
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