title: Crystal structures of Apo and GMP bound hypoxanthine-guanine phosphoribosyltransferase from Legionella pneumophila and the implications in gouty arthritis.
abstract: Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (EC 2.4.2.8) reversibly catalyzes the transfer of the 5-phophoribosyl group from 5-phosphoribosyl-alpha-1-pyrophosphate (PRPP) to hypoxanthine or guanine to form inosine monophosphate (IMP) or guanosine monophosphate (GMP) in the purine salvage pathway. To investigate the catalytic mechanism of this enzyme in the intracellular pathogen Legionella pneumophila, we determined the crystal structures of the L. pneumophila HGPRT (LpHGPRT) both in its apo-form and in complex with GMP. The structures reveal that LpHGPRT comprises a core domain and a hood domain which are packed together to create a cavity for GMP-binding and the enzymatic catalysis. The binding of GMP induces conformational changes of the stable loop II. This new binding site is closely related to the Gout arthritis-linked human HGPRT mutation site (Ser103Arg). Finally, these structures of LpHGPRT provide insights into the catalytic mechanism of HGPRT.
authors.affiliation: Institute of Health Sciences and School of Life Science, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Institute of Health Sciences and School of Life Science, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Gong
authors.affiliation: Institute of Health Sciences and School of Life Science, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: Institute of Health Sciences and School of Life Science, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Health Sciences and School of Life Science, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Qin
authors.affiliation: Institute of Health Sciences and School of Life Science, Anhui University, Hefei, Anhui 230601, China; Modern Experiment Technology Center, Anhui University, Hefei, Anhui 230601, China. Electronic address: ghh_ahu@foxmail.com.
authors.forename: Honghua
authors.initials: H
authors.lastname: Ge
mesh_terms: D015210:Arthritis, Gouty / Q000201:enzymology / Q000235:genetics; D001665:Binding Sites; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D006157:Guanosine Monophosphate / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000737:chemistry* / Q000378:metabolism; D016952:Legionella pneumophila / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D006157:Guanosine Monophosphate; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Crystal structure; GMP binding site; Hypoxanthine–guanine phosphoribosyltransferase; Legionella pneumophila