title: Crystal structure of Sus scrofa quinolinate phosphoribosyltransferase in complex with nicotinate mononucleotide.
abstract: We have determined the crystal structure of porcine quinolinate phosphoribosyltransferase (QAPRTase) in complex with nicotinate mononucleotide (NAMN), which is the first crystal structure of a mammalian QAPRTase with its reaction product. The structure was determined from protein obtained from the porcine kidney. Because the full protein sequence of porcine QAPRTase was not available in either protein or nucleotide databases, cDNA was synthesized using reverse transcriptase-polymerase chain reaction to determine the porcine QAPRTase amino acid sequence. The crystal structure revealed that porcine QAPRTases have a hexameric structure that is similar to other eukaryotic QAPRTases, such as the human and yeast enzymes. However, the interaction between NAMN and porcine QAPRTase was different from the interaction found in prokaryotic enzymes, such as those of Helicobacter pylori and Mycobacterium tuberculosis. The crystal structure of porcine QAPRTase in complex with NAMN provides a structural framework for understanding the unique properties of the mammalian QAPRTase active site and designing new antibiotics that are selective for the QAPRTases of pathogenic bacteria, such as H. pylori and M. tuberculosis.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science & Technology, Gwangju, Republic of Korea.
authors.forename: Hyung-Seop
authors.initials: HS
authors.lastname: Youn
authors.forename: Mun-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Gil Bu
authors.initials: GB
authors.lastname: Kang
authors.forename: Tae Gyun
authors.initials: TG
authors.lastname: Kim
authors.forename: Jung-Gyu
authors.initials: JG
authors.lastname: Lee
authors.forename: Jun Yop
authors.initials: JY
authors.lastname: An
authors.forename: Kyoung Ryoung
authors.initials: KR
authors.lastname: Park
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Lee
authors.forename: Jung Youn
authors.initials: JY
authors.lastname: Kang
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Song
authors.forename: Inju
authors.initials: I
authors.lastname: Park
authors.forename: Chunghee
authors.initials: C
authors.lastname: Cho
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fukuoka
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Eom
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000235:genetics; D016480:Helicobacter pylori / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000201:enzymology; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives* / Q000737:chemistry; D010430:Pentosyltransferases / Q000737:chemistry* / Q000235:genetics; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D013045:Species Specificity; D040681:Structural Homology, Protein; D013552:Swine; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
chemical_list: D018076:DNA, Complementary; D009537:Nicotinamide Mononucleotide; C002953:nicotinate mononucleotide; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)