5XCW
Crystal structure of M92A-M120A double mutant of O-acetyl-L-serine sulfhydrylase from Haemophilus influenzae
Summary for 5XCW
| Entry DOI | 10.2210/pdb5xcw/pdb |
| Related | 5XCN 5XCP |
| Descriptor | Cysteine synthase (2 entities in total) |
| Functional Keywords | pyridoxal phosphate binding, transferase activity, cysteine synthase activity, serine acetyl transferase binding protein, transferase |
| Biological source | Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) |
| Total number of polymer chains | 1 |
| Total formula weight | 37084.16 |
| Authors | Abhishek, K.,Kumaran, S. (deposition date: 2017-03-23, release date: 2018-05-02, Last modification date: 2023-11-22) |
| Primary citation | Kaushik, A.,Rahisuddin, R.,Saini, N.,Singh, R.P.,Kaur, R.,Kaul, S.,Kumaran, S. Molecular Mechanism of Selective Substrate Engagement and Inhibitor Dis-engagement of Cysteine Synthase. J.Biol.Chem., 2020 Cited by PubMed Abstract: O-acetyl serine sulfhydrylase (OASS), referred to as cysteine synthase (CS), synthesizes cysteine from O-acetyl serine (OAS) and sulfur in bacteria and plants. The inherent challenge for CS is to overcome 4 to 6 log-folds stronger affinity for its natural inhibitor, serine acetyltransferase (SAT), as compared with its affinity for substrate, OAS. Our recent study showed that CS employs a novel competitive-allosteric mechanism to selectively recruit its substrate in the presence of natural inhibitor. In this study, we trace the molecular features that control selective substrate recruitment. To generalize our findings, we used CS from three different bacteria (Haemophilus, Salmonella, and Mycobacterium) as our model systems and analyzed structural and substrate-binding features of wild-type CS and its ∼13 mutants. Results show that CS uses a noncatalytic residue, M120, located 20 Å away from the reaction center, to discriminate in favor of substrate. M120A and background mutants display significantly reduced substrate binding, catalytic efficiency, and inhibitor binding. Results shows that M120 favors the substrate binding by selectively enhancing the affinity for the substrate and disengaging the inhibitor by 20 to 286 and 5- to 3-folds, respectively. Together, M120 confers a net discriminative force in favor of substrate by 100- to 858-folds. PubMed: 33162395DOI: 10.1074/jbc.RA120.014490 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.89 Å) |
Structure validation
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