Crystal structure of Helicobacter pylori spermidine synthase: a Rossmann-like fold with a distinct active site.
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.
Lu
Po Kai
PK
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China.
Tsai
Jia-Yin
JY
Chien
Hsiang Yi
HY
Huang
Haimei
H
Chu
Chen-Hsi
CH
Sun
Yuh-Ju
YJ
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
D001426:Bacterial Proteins; D011436:Spermidine Synthase