6rq5
From Proteopedia
CYP121 in complex with 3,5-dimethyl dicyclotyrosine
Structural highlights
FunctionPublication Abstract from PubMedA series of analogues of cyclo(l-tyrosyl-l-tyrosine), the substrate of the Mycobacterium tuberculosis enzyme CYP121, have been synthesized and analyzed by UV-vis and electron paramagnetic resonance spectroscopy and by X-ray crystallography. The introduction of iodine substituents onto cyclo(l-tyrosyl-l-tyrosine) results in sub-muM binding affinity for the CYP121 enzyme and a complete shift to the high-spin state of the heme Fe(III). The introduction of halogens that are able to interact with heme groups is thus a feasible approach to the development of next-generation, tight binding inhibitors of the CYP121 enzyme, in the search for novel antitubercular compounds. Structure-Activity Relationships of cyclo(l-Tyrosyl-l-tyrosine) Derivatives Binding to Mycobacterium tuberculosis CYP121: Iodinated Analogues Promote Shift to High-Spin Adduct.,Rajput S, McLean KJ, Poddar H, Selvam IR, Nagalingam G, Triccas JA, Levy CW, Munro AW, Hutton CA J Med Chem. 2019 Nov 14;62(21):9792-9805. doi: 10.1021/acs.jmedchem.9b01199. Epub, 2019 Oct 31. PMID:31618032[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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