title: Crystal structure of a lysine biosynthesis enzyme, LysX, from Thermus thermophilus HB8.
abstract: The thermophilic bacterium Thermus thermophilus synthesizes lysine through the alpha-aminoadipate pathway, which uses alpha-aminoadipate as a biosynthetic intermediate of lysine. LysX is the essential enzyme in this pathway, and is believed to catalyze the acylation of alpha-aminoadipate. We have determined the crystal structures of LysX and its complex with ADP at 2.0A and 2.38A resolutions, respectively. LysX is composed of three alpha+beta domains, each composed of a four to five-stranded beta-sheet core flanked by alpha-helices. The C-terminal and central domains form an ATP-grasp fold, which is responsible for ATP binding. LysX has two flexible loop regions, which are expected to play an important role in substrate binding and protection. In spite of the low level of sequence identity, the overall fold of LysX is surprisingly similar to that of other ATP-grasp fold proteins, such as D-Ala:D-Ala ligase, PurT-encoded glycinamide ribonucleotide transformylase, glutathione synthetase, and synapsin I. In particular, they share a similar spatial arrangement of the amino acid residues around the ATP-binding site. This observation strongly suggests that LysX is an ATP-utilizing enzyme that shares a common evolutionary ancestor with other ATP-grasp fold proteins possessing a carboxylate-amine/thiol ligase activity.
authors.affiliation: RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama, 230-0045, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Marina N
authors.initials: MN
authors.lastname: Vassylyeva
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsuura
authors.forename: Shun ichi
authors.initials: Si
authors.lastname: Sekine
authors.forename: Kazumi
authors.initials: K
authors.lastname: Gotoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Seiki
authors.initials: S
authors.lastname: Kuramitsu
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Vassylyev
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D015074:2-Aminoadipic Acid / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D008239:Lysine / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D038601:Ribosomal Protein S6 / Q000378:metabolism; D016963:Thermus thermophilus / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D004798:Enzymes; D029968:Escherichia coli Proteins; C477978:LysX protein, T thermophilus; D038601:Ribosomal Protein S6; D015074:2-Aminoadipic Acid; D000255:Adenosine Triphosphate; D008239:Lysine