Sandbox Reserved 1056: Difference between revisions
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==Elucidation of ICL Structure Using Inhibitors== | ==Elucidation of ICL Structure Using Inhibitors== | ||
[[Image:Inhibitors57.png|400 px|right|thumb|Figure 5: Substrate inhibitors of Isocitrate Lyase]] | [[Image:Inhibitors57.png|400 px|right|thumb|Figure 5: Substrate inhibitors of Isocitrate Lyase]] | ||
The two inhibitors used to elucidate the structure of ICL were 3-nitropropionate and 3-bromopyruvate. The 3-nitropropionate was used to mimic the succinate, while the 3-bromopyruvate is used to mimic the glyoxylate. These two inhibitors have also been shown to be good inhibitors of isocitrate lyase in ''M. avium'' indicating that their inhibitory capacity is conserved across multiple species<ref name="ICL">PMID:10932251</ref>. A mutant isocitrate lyase C191S, in conjunction with the aforementioned substrate mimics, was used to elucidate the first high resolution crystal structure of ICL <ref name="ICL">PMID:10932251</ref>. Dehalogenated 3-bromopyruvate works to inhibit isocitrate lyase by forming a covalent bond with the | The two inhibitors used to elucidate the structure of ICL were 3-nitropropionate and 3-bromopyruvate. The 3-nitropropionate was used to mimic the succinate, while the 3-bromopyruvate is used to mimic the glyoxylate. These two inhibitors have also been shown to be good inhibitors of isocitrate lyase in ''M. avium'' indicating that their inhibitory capacity is conserved across multiple species<ref name="ICL">PMID:10932251</ref>. A mutant isocitrate lyase C191S, in conjunction with the aforementioned substrate mimics, was used to elucidate the first high resolution crystal structure of ICL <ref name="ICL">PMID:10932251</ref>. Dehalogenated 3-bromopyruvate works to inhibit isocitrate lyase by forming a covalent bond with the Ser191 in the active site. This 3-bromopyruvate occupies the same site that the succinate would occupy. The C191S mutant adopts a conformation almost identical to the CYS191 residue in the wild type indicating that this is an accurate depiction of the conformation. | ||
==Mechanism== | ==Mechanism== | ||