The aspartate kinase(AK)from Mycobacterium tuberculosis(Mtb)catalyzes the biosynthesis of aspartate family amino acids,including lysine,threonine,isoleucine and methionine.We determined the crystal structures of the r...The aspartate kinase(AK)from Mycobacterium tuberculosis(Mtb)catalyzes the biosynthesis of aspartate family amino acids,including lysine,threonine,isoleucine and methionine.We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone(referred to as MtbAKβ)and in complex with threonine(referred to as MtbAKβ-Thr)at resolutions of 2.6A and 2.0Å,respectively.MtbAKβ is composed of two perpendicular non-equivalent ACT domains[aspartate kinase,chorismate mutase,and TyrA(prephenate dehydrogenase)]per monomer.Each ACT domain contains two α helices and four antiparallel β strands.The structure of MtbAKβ shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum(referred to as CgAKβ),suggesting similar regulatory mechanisms.Biochemical assays in our study showed that MtbAK is inhibited by threonine.Based on crystal structure analysis,we discuss the regulatory mechanism of MtbAK.展开更多
基金supported by the National Basic Research Program(973 Program)(Grant Nos.2011CB915501 and 2011CB910304)National Major Project(Grant Nos.2009ZX10004-304 and 2009ZX10004-802).
文摘The aspartate kinase(AK)from Mycobacterium tuberculosis(Mtb)catalyzes the biosynthesis of aspartate family amino acids,including lysine,threonine,isoleucine and methionine.We determined the crystal structures of the regulatory subunit of aspartate kinase from Mtb alone(referred to as MtbAKβ)and in complex with threonine(referred to as MtbAKβ-Thr)at resolutions of 2.6A and 2.0Å,respectively.MtbAKβ is composed of two perpendicular non-equivalent ACT domains[aspartate kinase,chorismate mutase,and TyrA(prephenate dehydrogenase)]per monomer.Each ACT domain contains two α helices and four antiparallel β strands.The structure of MtbAKβ shares high similarity with the regulatory subunit of the aspartate kinase from Corynebacterium glutamicum(referred to as CgAKβ),suggesting similar regulatory mechanisms.Biochemical assays in our study showed that MtbAK is inhibited by threonine.Based on crystal structure analysis,we discuss the regulatory mechanism of MtbAK.
