title: Crystal structure of Helicobacter pylori spermidine synthase: a Rossmann-like fold with a distinct active site.
abstract: Spermidine synthase (putrescine aminopropyltransferase, PAPT) catalyzes the transfer of the aminopropyl group from decarboxylated S-adenosylmethionine to putrescine during spermidine biosynthesis. Helicobacter pylori PAPT (HpPAPT) has a low sequence identity with other PAPTs and lacks the signature sequence found in other PAPTs. The crystal structure of HpPAPT, determined by multiwavelength anomalous dispersion, revealed an N-terminal beta-stranded domain and a C-terminal Rossmann-like domain. Structural comparison with other PAPTs showed that HpPAPT has a unique binding pocket between two domains, numerous non-conserved residues, a less acidic electrostatic surface potential, and a large buried space within the structure. HpPAPT lacks the gatekeeping loop that facilitates substrate binding in other PAPTs. PAPTs are essential for bacterial cell viability; thus, HpPAPT may be a potential antimicrobial drug target for H. pylori owing to its characteristic PAPT sequence and distinct conformation.
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China.
authors.forename: Po Kai
authors.initials: PK
authors.lastname: Lu
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Tsai
authors.forename: Hsiang Yi
authors.initials: HY
authors.lastname: Chien
authors.forename: Haimei
authors.initials: H
authors.lastname: Huang
authors.forename: Chen-Hsi
authors.initials: CH
authors.lastname: Chu
authors.forename: Yuh-Ju
authors.initials: YJ
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray / Q000379:methods; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D011436:Spermidine Synthase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D011436:Spermidine Synthase