Alpha-D-phosphohexomutase superfamily

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Alpha-D-phosphohexomutase
Identifiers
Symbol ?
InterPro IPR005841
CDD cd03084

The alpha-D-phosphohexomutases are a large superfamily of enzymes, with members in all three domains of life. Enzymes from this superfamily are ubiquitous in organisms from E. Coli to humans, and catalyze a phosphoryl transfer reaction on a phosphosugar substrate. Four well studied subgroups in the superfamily are:

  1. Phosphoglucomutase (PGM)
  2. Phosphoglucomutase/Phosphomannomutase (PGM/PMM)
  3. Phosphoglucosamine mutase (PNGM)
  4. Phosphoaceytlglucosamine mutase (PAGM)

Other enzymes in the superfamily are known to act as glucose 1,6-bisphoshpate synthases and phosphopentomutases.

Background[edit]

A number of proteins in the superfamily have been characterized functionally and structurally. This table illustrates different members of the superfamily.

Catalytic Reaction[edit]

The enzymes in the superfamily typically catalyze the reversible conversion of 1-phosphosugars to 6-phosphosugars. The reaction proceeds via a bisphosphorylated sugar intermediate. The active form of the enzyme is phosphorylated at a conserved serine residue in the active site, and also requires a bound metal ion, typically Mg2+ for full activity. The initial phosphoryl transfer takes place from the phosphoserine to the substrate, creating a bisphosphorylated sugar intermediate. This is followed by a second phosphoryl transfer from the substrate back to enzyme, producing product and regenerating the active form of the enzyme.[36]

Structure & Oligomeric State[edit]

Structures of multiple enzymes have been determined through X-ray crystallography. In general, they share a very similar topology. With a heart-shape and four domains (see image below), most enzymes appear to be monomers.

A superposition of four enzymes from the alpha D phosphohexomutase superfamily, one from each subgroup, demonstrating the structural similarity of all members in the superfamily.

However some are known to exist as dimers or tetramers in solution. Eleven crystal structures for this superfamily have been determined thus far, six of which are likely oligomers. Two distinct dimers and one tetrameric arrangement has been documented.[37]

Subgroups[edit]

There are 4 well characterized enzyme subgroups in this superfamily, which differ in their specificity for the sugar moeiety of the substrate.

PGM[edit]

Phosphoglucomutase (PGM) converts D-glucose-1-phosphate into D-glucose-6-phosphate, participating in glucose breakdown & synthesis. Bacterial and eukaryotic organisms are known to have PGM enzymes, with 415 representatives currently listed in the PIR database.[38] Among bacteria, Salmonella typhimurium and Thermus thermophilus have PGM enzymes of characterized 3D structure. In eukaryotes, PGM enzymes from Oryctolagus cuniculus (rabbit) and Paramecium tetraurelia also have been structurally characterized. The highest resolution structure is from Salmonella typhimurium (1.7 A), with PDB ID 3na5. In addition, biochemical studies have shown that PGM from S. typhimurium is a dimer in solution based on analytical ultracentrifugation and small-angle X-ray scattering (SAXS). [39]

PMM/PGM[edit]

Phosphoglucomutase/phosphomannomutase (PGM/PMM)- Enzymes from this subgroup can use either mannose or glucose-based phosphosugar substrates with equal efficiency. PMM/PGM enzymes are found mainly in bacterial organisms, with a total of 1,331 representatives currently listed in the PIR database.[40] These enzymes are involved in the biosynthesis of many different carbohydrates and glycolipids, which vary depending on the organism. The best studied enzyme from this subgroup is from the bacterium, Pseudomonas aeruginosa, where PMM/PGM participate in multiple biosynthetic pathways including those of lipopolysaccharide, alginate and rhamnoplipid.

Structural studies of P. aeruginosa PMM/PGM by X-ray crystallography have been conducted as both apo-enzyme and as protein-ligand complexes. Based on these studies, it has been seen that when the sugar substrate binds to the enzyme there is a rotation in the C-terminal domain of the protein. This changes the active site from an open cleft in the apo-enzyme into a nearly solvent inaccessible pocket. This theme of conformational flexibility, particularly with regard to the C-terminal domain of these enzymes, has been observed in multiple proteins in the superfamily.

PNGM[edit]

Phosphoglucosamine mutase (PNGM) participates in the biosynthesis of UDP-N-Acetylglucosamine (UDP-GlcNAc). This bacterial enzyme has been conserved throughout evolution and is involved in the cytoplasmic steps of peptidoglycan biosynthesis, which is essential for bacterial survival and is also not present in humans.[41]

PAGM[edit]

Phosphoacetylglucosamine mutase (PAGM)- To date, this subgroup contains 178 members, with all known being eukaryotic.[42] There is only one known organism with known structure, it is Candida albicans. Like PNGM, it is involved in the biosynthesis of UDP-N-acetylglucosamine. UDP-GlcNAc is a UDP sugar that works as a biosynthetic precursor of glycoproteins, mucopolysaccharides, and the cell wall of bacteria. AGM1, a characterized structure of PAGM, catalyzes the conversion of N-acetylglucosamine 6-phosphate to N-acetylglucosamine 1-phosphate. AGM1 structure was determined from Candida albicans in the apoform and complex forms with substrate and product. Like other enzymes in the superfamily, it has four domains, with two additional beta-strands in domain four and a circular permutation in domain 1.[43]

References[edit]

  1. ^ Zhou D, Stephens DS, Gibson BW, Engstrom JJ, McAllister CF, Lee FK, Apicella MA (April 1994). "Lipooligosaccharide biosynthesis in pathogenic Neisseria. Cloning, identification, and characterization of the phosphoglucomutase gene". The Journal of Biological Chemistry. 269 (15): 11162–9. PMID 8157643. 
  2. ^ Sandlin RC, Stein DC (May 1994). "Role of phosphoglucomutase in lipooligosaccharide biosynthesis in Neisseria gonorrhoeae". Journal of Bacteriology. 176 (10): 2930–7. PMID 8188595. 
  3. ^ Monteiro MA, Fortuna-Nevin M, Farley J, Pavliak V (November 2003). "Phase-variation of the truncated lipo-oligosaccharide of Neisseria meningitidis NMB phosphoglucomutase isogenic mutant NMB-R6". Carbohydrate Research. 338 (24): 2905–12. PMID 14667712. 
  4. ^ Gründling A, Schneewind O (March 2007). "Genes required for glycolipid synthesis and lipoteichoic acid anchoring in Staphylococcus aureus". Journal of Bacteriology. 189 (6): 2521–30. doi:10.1128/jb.01683-06. PMC 1899383Freely accessible. PMID 17209021. 
  5. ^ Jolly L, Wu S, van Heijenoort J, de Lencastre H, Mengin-Lecreulx D, Tomasz A (September 1997). "The femR315 gene from Staphylococcus aureus, the interruption of which results in reduced methicillin resistance, encodes a phosphoglucosamine mutase". Journal of Bacteriology. 179 (17): 5321–5. PMID 9286983. 
  6. ^ Bizzini A, Majcherczyk P, Beggah-Möller S, Soldo B, Entenza JM, Gaillard M, Moreillon P, Lazarevic V (February 2007). "Effects of alpha-phosphoglucomutase deficiency on cell wall properties and fitness in Streptococcus gordonii". Microbiology. 153 (Pt 2): 490–8. doi:10.1099/mic.0.29256-0. PMID 17259620. 
  7. ^ Shimazu K, Takahashi Y, Uchikawa Y, Shimazu Y, Yajima A, Takashima E, Aoba T, Konishi K (July 2008). "Identification of the Streptococcus gordonii glmM gene encoding phosphoglucosamine mutase and its role in bacterial cell morphology, biofilm formation, and sensitivity to antibiotics". FEMS Immunology and Medical Microbiology. 53 (2): 166–77. doi:10.1111/j.1574-695X.2008.00410.x. PMID 18462386. 
  8. ^ Yajima A, Takahashi Y, Shimazu K, Urano-Tashiro Y, Uchikawa Y, Karibe H, Konishi K (August 2009). "Contribution of phosphoglucosamine mutase to the resistance of Streptococcus gordonii DL1 to polymorphonuclear leukocyte killing". FEMS Microbiology Letters. 297 (2): 196–202. doi:10.1111/j.1574-6968.2009.01673.x. PMID 19552711. 
  9. ^ Shimazu K, Takahashi Y, Karibe H, Mitsuhashi F, Konishi K (January 2012). "Contribution of phosphoglucosamine mutase to determination of bacterial cell morphology in Streptococcus gordonii". Odontology. 100 (1): 28–33. doi:10.1007/s10266-011-0026-1. PMID 21567120. 
  10. ^ Buchanan JT, Stannard JA, Lauth X, Ostland VE, Powell HC, Westerman ME, Nizet V (October 2005). "Streptococcus iniae phosphoglucomutase is a virulence factor and a target for vaccine development". Infection and Immunity. 73 (10): 6935–44. doi:10.1128/iai.73.10.6935-6944.2005. PMC 1230984Freely accessible. PMID 16177373. 
  11. ^ Liu XD, Duan J, Guo LH (August 2009). "Role of phosphoglucosamine mutase on virulence properties of Streptococcus mutans". Oral Microbiology and Immunology. 24 (4): 272–7. doi:10.1111/j.1399-302x.2009.00503.x. PMID 19572887. 
  12. ^ Hardy GG, Caimano MJ, Yother J (April 2000). "Capsule biosynthesis and basic metabolism in Streptococcus pneumoniae are linked through the cellular phosphoglucomutase". Journal of Bacteriology. 182 (7): 1854–63. doi:10.1128/jb.182.7.1854-1863.2000. PMID 10714989. 
  13. ^ Hardy GG, Magee AD, Ventura CL, Caimano MJ, Yother J (April 2001). "Essential role for cellular phosphoglucomutase in virulence of type 3 Streptococcus pneumoniae". Infection and Immunity. 69 (4): 2309–17. doi:10.1128/iai.69.4.2309-2317.2001. PMC 98160Freely accessible. PMID 11254588. 
  14. ^ McCarthy TR, Torrelles JB, MacFarlane AS, Katawczik M, Kutzbach B, Desjardin LE, Clegg S, Goldberg JB, Schlesinger LS (November 2005). "Overexpression of Mycobacterium tuberculosis manB, a phosphomannomutase that increases phosphatidylinositol mannoside biosynthesis in Mycobacterium smegmatis and mycobacterial association with human macrophages". Molecular Microbiology. 58 (3): 774–90. doi:10.1111/j.1365-2958.2005.04862.x. PMID 16238626. 
  15. ^ Li S, Kang J, Yu W, Zhou Y, Zhang W, Xin Y, Ma Y (2012). "Identification of M. tuberculosis Rv3441c and M. smegmatis MSMEG_1556 and essentiality of M. smegmatis MSMEG_1556". PLOS One. 7 (8): e42769. doi:10.1371/journal.pone.0042769. PMC 3414508Freely accessible. PMID 22905172. 
  16. ^ West NP, Jungnitz H, Fitter JT, McArthur JD, Guzmán CA, Walker MJ (August 2000). "Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide biosynthesis and virulence". Infection and Immunity. 68 (8): 4673–80. doi:10.1128/iai.68.8.4673-4680.2000. PMC 98408Freely accessible. PMID 10899872. 
  17. ^ Pei J, Ficht TA (January 2004). "Brucella abortus rough mutants are cytopathic for macrophages in culture". Infection and Immunity. 72 (1): 440–50. doi:10.1128/iai.72.1.440-450.2004. PMC 343953Freely accessible. PMID 14688125. 
  18. ^ Ugalde JE, Comerci DJ, Leguizamón MS, Ugalde RA (November 2003). "Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live rough-phenotype vaccine". Infection and Immunity. 71 (11): 6264–9. doi:10.1128/iai.71.11.6264-6269.2003. PMC 219583Freely accessible. PMID 14573645. 
  19. ^ Ugalde JE, Czibener C, Feldman MF, Ugalde RA (October 2000). "Identification and characterization of the Brucella abortus phosphoglucomutase gene: role of lipopolysaccharide in virulence and intracellular multiplication". Infection and Immunity. 68 (10): 5716–23. doi:10.1128/iai.68.10.5716-5723.2000. PMID 10992476. 
  20. ^ Paixão TA, Roux CM, den Hartigh AB, Sankaran-Walters S, Dandekar S, Santos RL, Tsolis RM (October 2009). "Establishment of systemic Brucella melitensis infection through the digestive tract requires urease, the type IV secretion system, and lipopolysaccharide O antigen". Infection and Immunity. 77 (10): 4197–208. doi:10.1128/iai.00417-09. PMC 2747930Freely accessible. PMID 19651862. 
  21. ^ Lu M, Kleckner N (September 1994). "Molecular cloning and characterization of the pgm gene encoding phosphoglucomutase of Escherichia coli". Journal of Bacteriology. 176 (18): 5847–51. PMID 8083177. 
  22. ^ Mengin-Lecreulx D, van Heijenoort J (January 1996). "Characterization of the essential gene glmM encoding phosphoglucosamine mutase in Escherichia coli". The Journal of Biological Chemistry. 271 (1): 32–9. doi:10.1074/jbc.271.1.32. PMID 8550580. 
  23. ^ Grass S, Buscher AZ, Swords WE, Apicella MA, Barenkamp SJ, Ozchlewski N, St Geme JW (May 2003). "The Haemophilus influenzae HMW1 adhesin is glycosylated in a process that requires HMW1C and phosphoglucomutase, an enzyme involved in lipooligosaccharide biosynthesis". Molecular Microbiology. 48 (3): 737–51. doi:10.1046/j.1365-2958.2003.03450.x. PMID 12694618. 
  24. ^ Swords WE, Buscher BA, Ver Steeg Ii K, Preston A, Nichols WA, Weiser JN, Gibson BW, Apicella MA (July 2000). "Non-typeable Haemophilus influenzae adhere to and invade human bronchial epithelial cells via an interaction of lipooligosaccharide with the PAF receptor". Molecular Microbiology. 37 (1): 13–27. doi:10.1046/j.1365-2958.2000.01952.x. PMID 10931302. 
  25. ^ De Reuse H, Labigne A, Mengin-Lecreulx D (June 1997). "The Helicobacter pylori ureC gene codes for a phosphoglucosamine mutase". Journal of Bacteriology. 179 (11): 3488–93. PMID 9171391. 
  26. ^ Goldberg JB, Coyne MJ, Neely AN, Holder IA (October 1995). "Avirulence of a Pseudomonas aeruginosa algC mutant in a burned-mouse model of infection". Infection and Immunity. 63 (10): 4166–9. PMID 7558335. 
  27. ^ Tang HB, DiMango E, Bryan R, Gambello M, Iglewski BH, Goldberg JB, Prince A (January 1996). "Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection". Infection and Immunity. 64 (1): 37–43. PMID 8557368. 
  28. ^ Tavares IM, Leitão JH, Sá-Correia I (March 2003). "Chromosomal organization and transcription analysis of genes in the vicinity of Pseudomonas aeruginosa glmM gene encoding phosphoglucosamine mutase". Biochemical and Biophysical Research Communications. 302 (2): 363–71. doi:10.1016/s0006-291x(03)00169-4. PMID 12604356. 
  29. ^ Paterson GK, Cone DB, Peters SE, Maskell DJ (October 2009). "The enzyme phosphoglucomutase (Pgm) is required by Salmonella enterica serovar Typhimurium for O-antigen production, resistance to antimicrobial peptides and in vivo fitness". Microbiology. 155 (Pt 10): 3403–10. doi:10.1099/mic.0.029553-0. PMID 19589833. 
  30. ^ Rathi B, Sarangi AN, Trivedi N (October 2009). "Genome subtraction for novel target definition in Salmonella typhi". Bioinformation. 4 (4): 143–50. doi:10.6026/97320630004143. PMID 20198190. 
  31. ^ McKay GA, Woods DE, MacDonald KL, Poole K (June 2003). "Role of phosphoglucomutase of Stenotrophomonas maltophilia in lipopolysaccharide biosynthesis, virulence, and antibiotic resistance". Infection and Immunity. 71 (6): 3068–75. doi:10.1128/iai.71.6.3068-3075.2003. PMID 12761084. 
  32. ^ Liaw SJ, Lee YL, Hsueh PR (February 2010). "Multidrug resistance in clinical isolates of Stenotrophomonas maltophilia: roles of integrons, efflux pumps, phosphoglucomutase (SpgM), and melanin and biofilm formation". International Journal of Antimicrobial Agents. 35 (2): 126–30. doi:10.1016/j.ijantimicag.2009.09.015. PMID 19926255. 
  33. ^ Kim SH, Ahn SH, Lee JH, Lee EM, Kim NH, Park KJ, Kong IS (October 2003). "Genetic analysis of phosphomannomutase/phosphoglucomutase from Vibrio furnissii and characterization of its role in virulence". Archives of Microbiology. 180 (4): 240–50. doi:10.1007/s00203-003-0582-z. PMID 12904831. 
  34. ^ Chiang SL, Mekalanos JJ (February 1999). "rfb mutations in Vibrio cholerae do not affect surface production of toxin-coregulated pili but still inhibit intestinal colonization". Infection and Immunity. 67 (2): 976–80. PMID 9916119. 
  35. ^ Felek S, Muszyński A, Carlson RW, Tsang TM, Hinnebusch BJ, Krukonis ES (March 2010). "Phosphoglucomutase of Yersinia pestis is required for autoaggregation and polymyxin B resistance". Infection and Immunity. 78 (3): 1163–75. doi:10.1128/iai.00997-09. PMID 20028810. 
  36. ^ Shackelford GS, Regni CA, Beamer LJ (August 2004). "Evolutionary trace analysis of the alpha-D-phosphohexomutase superfamily". Protein Science. 13 (8): 2130–8. doi:10.1110/ps.04801104. PMC 2279825Freely accessible. PMID 15238632. 
  37. ^ Luebbering EK, Mick J, Singh RK, Tanner JJ, Mehra-Chaudhary R, Beamer LJ (November 2012). "Conservation of functionally important global motions in an enzyme superfamily across varying quaternary structures". Journal of Molecular Biology. 423 (5): 831–46. doi:10.1016/j.jmb.2012.08.013. PMID 22935436. 
  38. ^ "Summary Report for PIRSF001493". 
  39. ^ Mehra-Chaudhary R, Mick J, Tanner JJ, Henzl MT, Beamer LJ (April 2011). "Crystal structure of a bacterial phosphoglucomutase, an enzyme involved in the virulence of multiple human pathogens". Proteins. 79 (4): 1215–29. doi:10.1002/prot.22957. PMID 21246636. 
  40. ^ "Summary Report for PIRSF005849". 
  41. ^ Mehra-Chaudhary R, Mick J, Beamer LJ (August 2011). "Crystal structure of Bacillus anthracis phosphoglucosamine mutase, an enzyme in the peptidoglycan biosynthetic pathway". Journal of Bacteriology. 193 (16): 4081–7. doi:10.1128/jb.00418-11. PMID 21685296. 
  42. ^ "Summary report for PIRSF016408". 
  43. ^ Nishitani Y, Maruyama D, Nonaka T, Kita A, Fukami TA, Mio T, Yamada-Okabe H, Yamada-Okabe T, Miki K (July 2006). "Crystal structures of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, and its substrate and product complexes". The Journal of Biological Chemistry. 281 (28): 19740–7. doi:10.1074/jbc.m600801200. PMID 16651269.