Isoniazid inhibits human erythroid 5-aminolevulinate synthase: Molecular mechanism and tolerance study with four X-linked protoporphyria patients

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• 作者：Erica J. Fratz-Berilla^a ; Leonid Breydo^a ; ^b ; Laurent Gouya^c ; ^d ; ^e ; Hervé ; Puy^c ; ^d ; ^e ; Vladimir N. Uversky^a ; ^b ; Gloria C. Ferreira^a ; ^f ; ^{gferreir@health.usf.edu}
• 关键词：ALA ; 5-aminolevulinic acid ; ALAS1 ; non-specific isoform of 5-aminolevulinate synthase ; ALAS2 ; erythroid-specific isoform of 5-aminolevulinate synthase ; mALAS2 ; erythroid-specific isoform of murine 5-aminolevulinate synthase ; ΔmALAS2 ; erythroid-specific isoform of 5-aminolevulinate synthase with an N-terminal truncation ; hALAS1 ; non-specific isoform of human 5-aminolevulinate synthase ; hALAS2 ; erythroid-specific isoform of human 5-aminolevulinate synthase ; PLP ; pyridoxal 5&prime ; -phosphate ; SDS-P
• 刊名：Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：1863
• 期：2
• 页码：428-439
• 全文大小：1279 K
• 卷排序：1863

文摘

Isoniazid (INH) directly inhibits erythroid aminolevulinate synthase (ALAS2). INH alters the ALAS2 tertiary structure and hinders PLP cofactor binding to ALAS2. Ex vivo inhibition of ALAS2 by INH is reversed by PLP and PMP, but not pyridoxine.