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PDBsum entry 1b8o

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protein ligands metals links
Transferase PDB id
1b8o
Jmol
Contents
Protein chain
280 a.a. *
Ligands
PO4
IMH
Metals
_MG
Waters ×197
* Residue conservation analysis
PDB id:
1b8o
Name: Transferase
Title: Purine nucleoside phosphorylase
Structure: Purine nucleoside phosphorylase. Chain: a. Other_details: complexed with transition-state analogue 1,4 1,4-imino-1-(s)-(9-deazahypoxanthin-9-yl)-d-ribitol
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: spleen
Biol. unit: Trimer (from PQS)
Resolution:
1.50Å     R-factor:   0.184     R-free:   0.232
Authors: A.A.Fedorov,G.A.Kicska,E.V.Fedorov,W.Shi,P.C.Tyler,R.H.Furne V.L.Schramm,S.C.Almo
Key ref:
A.Fedorov et al. (2001). Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis. Biochemistry, 40, 853-860. PubMed id: 11170405 DOI: 10.1021/bi002499f
Date:
02-Feb-99     Release date:   08-Feb-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P55859  (PNPH_BOVIN) -  Purine nucleoside phosphorylase
Seq:
Struc:
289 a.a.
280 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.1  - Purine-nucleoside phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate
2. Purine deoxynucleoside + phosphate = purine + 2'-deoxy-alpha-D-ribose 1-phosphate
Purine nucleoside
Bound ligand (Het Group name = IMH)
matches with 60.87% similarity
+
phosphate
Bound ligand (Het Group name = PO4)
corresponds exactly
= purine
+ alpha-D-ribose 1-phosphate
Purine deoxynucleoside
+ phosphate
= purine
+ 2'-deoxy-alpha-D-ribose 1-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     nucleobase-containing compound metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi002499f Biochemistry 40:853-860 (2001)
PubMed id: 11170405  
 
 
Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis.
A.Fedorov, W.Shi, G.Kicska, E.Fedorov, P.C.Tyler, R.H.Furneaux, J.C.Hanson, G.J.Gainsford, J.Z.Larese, V.L.Schramm, S.C.Almo.
 
  ABSTRACT  
 
Immucillin-H [ImmH; (1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol] is a 23 pM inhibitor of bovine purine nucleoside phosphorylase (PNP) specifically designed as a transition state mimic [Miles, R. W., Tyler, P. C., Furneaux, R. H., Bagdassarian, C. K., and Schramm, V. L. (1998) Biochemistry 37, 8615-8621]. Cocrystals of PNP and the inhibitor are used to provide structural information for each step through the reaction coordinate of PNP. The X-ray crystal structure of free ImmH was solved at 0.9 A resolution, and a complex of PNP.ImmH.PO(4) was solved at 1.5 A resolution. These structures are compared to previously reported complexes of PNP with substrate and product analogues in the catalytic sites and with the experimentally determined transition state structure. Upon binding, ImmH is distorted to a conformation favoring ribosyl oxocarbenium ion formation. Ribosyl destabilization and transition state stabilization of the ribosyl oxocarbenium ion occur from neighboring group interactions with the phosphate anion and the 5'-hydroxyl of the ribosyl group. Leaving group activation of hypoxanthine involves hydrogen bonds to O6, N1, and N7 of the purine ring. Ordered water molecules provide a proton transfer bridge to O6 and N7 and permit reversible formation of these hydrogen bonds. Contacts between PNP and catalytic site ligands are shorter in the transition state analogue complex of PNP.ImmH.PO(4) than in the Michaelis complexes of PNP.inosine.SO(4) or PNP.hypoxanthine.ribose 1-PO(4). Reaction coordinate motion is dominated by translation of the carbon 1' of ribose between relatively fixed phosphate and purine groups. Purine and pyrimidine phosphoribosyltransferases and nucleoside N-ribosyl hydrolases appear to operate by a similar mechanism.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20714463 D.J.Wardrop, and S.L.Waidyarachchi (2010).
Synthesis and biological activity of naturally occurring α-glucosidase inhibitors.
  Nat Prod Rep, 27, 1431-1468.  
20525731 D.P.Nannemann, K.W.Kaufmann, J.Meiler, and B.O.Bachmann (2010).
Design and directed evolution of a dideoxy purine nucleoside phosphorylase.
  Protein Eng Des Sel, 23, 607-616.  
20203397 G.J.Gainsford, R.H.Furneaux, P.C.Tyler, A.Sauve, and V.L.Shramm (2010).
A synchrotron radiation study of the one-dimensional complex of sodium with (1S)-N-carboxylato-1-(9-deazaadenin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol, a member of the 'immucillin' family.
  Acta Crystallogr C, 66, m65-m68.  
20170081 H.Deng, R.Callender, V.L.Schramm, and C.Grubmeyer (2010).
Pyrophosphate activation in hypoxanthine--guanine phosphoribosyltransferase with transition state analogue.
  Biochemistry, 49, 2705-2714.  
20057051 H.M.Pereira, M.M.Rezende, M.S.Castilho, G.Oliva, and R.C.Garratt (2010).
Adenosine binding to low-molecular-weight purine nucleoside phosphorylase: the structural basis for recognition based on its complex with the enzyme from Schistosoma mansoni.
  Acta Crystallogr D Biol Crystallogr, 66, 73-79.
PDB codes: 3e9r 3f8w 3faz 3fnq
20212140 M.C.Ho, W.Shi, A.Rinaldo-Matthis, P.C.Tyler, G.B.Evans, K.Clinch, S.C.Almo, and V.L.Schramm (2010).
Four generations of transition-state analogues for human purine nucleoside phosphorylase.
  Proc Natl Acad Sci U S A, 107, 4805-4812.  
19819904 R.Takahashi, S.Nakamura, T.Nakazawa, K.Minoura, T.Yoshida, Y.Nishi, Y.Kobayashi, and T.Ohkubo (2010).
Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase.
  J Biochem, 147, 95.
PDB codes: 2e5b 2e5c 2e5d
19425594 A.A.Edwards, J.M.Mason, K.Clinch, P.C.Tyler, G.B.Evans, and V.L.Schramm (2009).
Altered enthalpy-entropy compensation in picomolar transition state analogues of human purine nucleoside phosphorylase.
  Biochemistry, 48, 5226-5238.  
19575810 A.Chaikuad, and R.L.Brady (2009).
Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases.
  BMC Struct Biol, 9, 42.
PDB codes: 3emv 3enz
19666527 E.S.Burgos, M.C.Ho, S.C.Almo, and V.L.Schramm (2009).
A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT.
  Proc Natl Acad Sci U S A, 106, 13748-13753.
PDB codes: 3dgr 3dhd 3dhf 3dkj 3dkl
19152365 F.Fontaine, S.Cross, G.Plasencia, M.Pastor, and I.Zamora (2009).
SHOP: a method for structure-based fragment and scaffold hopping.
  ChemMedChem, 4, 427-439.  
19115304 M.Berg, G.Bal, A.Goeminne, P.Van der Veken, W.Versées, J.Steyaert, A.Haemers, and K.Augustyns (2009).
Synthesis of bicyclic N-arylmethyl-substituted iminoribitol derivatives as selective nucleoside hydrolase inhibitors.
  ChemMedChem, 4, 249-260.  
19778725 M.Ghanem, A.S.Murkin, and V.L.Schramm (2009).
Ribocation transition state capture and rebound in human purine nucleoside phosphorylase.
  Chem Biol, 16, 971-979.  
19191546 M.Ghanem, N.Zhadin, R.Callender, and V.L.Schramm (2009).
Loop-tryptophan human purine nucleoside phosphorylase reveals submillisecond protein dynamics.
  Biochemistry, 48, 3658-3668.  
19620996 S.D.Schwartz, and V.L.Schramm (2009).
Enzymatic transition states and dynamic motion in barrier crossing.
  Nat Chem Biol, 5, 551-558.  
18154341 A.Rinaldo-Matthis, A.S.Murkin, U.A.Ramagopal, K.Clinch, S.P.Mee, G.B.Evans, P.C.Tyler, R.H.Furneaux, S.C.Almo, and V.L.Schramm (2008).
L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase.
  J Am Chem Soc, 130, 842-844.
PDB codes: 2q7o 3bgs
19059104 R.G.Matthews, M.Koutmos, and S.Datta (2008).
Cobalamin-dependent and cobamide-dependent methyltransferases.
  Curr Opin Struct Biol, 18, 658-666.  
18234834 S.Saen-Oon, M.Ghanem, V.L.Schramm, and S.D.Schwartz (2008).
Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase.
  Biophys J, 94, 4078-4088.  
18946041 S.Saen-Oon, S.Quaytman-Machleder, V.L.Schramm, and S.D.Schwartz (2008).
Atomic detail of chemical transformation at the transition state of an enzymatic reaction.
  Proc Natl Acad Sci U S A, 105, 16543-16548.  
18801467 S.W.Ragsdale, and E.Pierce (2008).
Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation.
  Biochim Biophys Acta, 1784, 1873-1898.  
18804699 S.W.Ragsdale (2008).
Catalysis of methyl group transfers involving tetrahydrofolate and B(12).
  Vitam Horm, 79, 293-324.  
17407325 A.S.Murkin, M.R.Birck, A.Rinaldo-Matthis, W.Shi, E.A.Taylor, S.C.Almo, and V.L.Schramm (2007).
Neighboring group participation in the transition state of human purine nucleoside phosphorylase.
  Biochemistry, 46, 5038-5049.
PDB codes: 2a0w 2a0x 2a0y 2oc4 2oc9 2on6
17172470 T.I.Doukov, H.Hemmi, C.L.Drennan, and S.W.Ragsdale (2007).
Structural and kinetic evidence for an extended hydrogen-bonding network in catalysis of methyl group transfer. Role of an active site asparagine residue in activation of methyl transfer by methyltransferases.
  J Biol Chem, 282, 6609-6618.
PDB codes: 2e7f 2ogy
17690091 V.L.Schramm (2007).
Enzymatic transition state theory and transition state analogue design.
  J Biol Chem, 282, 28297-28300.  
17869163 V.L.Schramm (2007).
Binding isotope effects: boon and bane.
  Curr Opin Chem Biol, 11, 529-536.  
16734442 E.A.Taylor Ringia, P.C.Tyler, G.B.Evans, R.H.Furneaux, A.S.Murkin, and V.L.Schramm (2006).
Transition state analogue discrimination by related purine nucleoside phosphorylases.
  J Am Chem Soc, 128, 7126-7127.  
16636277 E.S.Radisky, J.M.Lee, C.J.Lu, and D.E.Koshland (2006).
Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
  Proc Natl Acad Sci U S A, 103, 6835-6840.
PDB codes: 2age 2agg 2agi 2ah4
16525558 K.Clinch, G.B.Evans, G.W.Fleet, R.H.Furneaux, S.W.Johnson, D.H.Lenz, S.P.Mee, P.R.Rands, V.L.Schramm, E.A.Taylor Ringia, and P.C.Tyler (2006).
Syntheses and bio-activities of the L-enantiomers of two potent transition state analogue inhibitors of purine nucleoside phosphorylases.
  Org Biomol Chem, 4, 1131-1139.  
17154531 K.S.Champagne, E.Piscitelli, and C.S.Francklyn (2006).
Substrate recognition by the hetero-octameric ATP phosphoribosyltransferase from Lactococcus lactis.
  Biochemistry, 45, 14933-14943.  
15961383 A.Lewandowicz, E.A.Ringia, L.M.Ting, K.Kim, P.C.Tyler, G.B.Evans, O.V.Zubkova, S.Mee, G.F.Painter, D.H.Lenz, R.H.Furneaux, and V.L.Schramm (2005).
Energetic mapping of transition state analogue interactions with human and Plasmodium falciparum purine nucleoside phosphorylases.
  J Biol Chem, 280, 30320-30328.  
16239721 A.V.Toms, W.Wang, Y.Li, B.Ganem, and S.E.Ealick (2005).
Novel multisubstrate inhibitors of mammalian purine nucleoside phosphorylase.
  Acta Crystallogr D Biol Crystallogr, 61, 1449-1458.
PDB codes: 2ai1 2ai2 2ai3
16023348 E.K.Jaffe (2005).
Morpheeins--a new structural paradigm for allosteric regulation.
  Trends Biochem Sci, 30, 490-497.  
15983407 F.Canduri, R.G.Silva, D.M.dos Santos, M.S.Palma, L.A.Basso, D.S.Santos, and W.F.de Azevedo (2005).
Structure of human PNP complexed with ligands.
  Acta Crystallogr D Biol Crystallogr, 61, 856-862.
PDB codes: 1rfg 1v41 1v45
16051603 K.S.Champagne, M.Sissler, Y.Larrabee, S.Doublié, and C.S.Francklyn (2005).
Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog.
  J Biol Chem, 280, 34096-34104.
PDB codes: 1z7m 1z7n
15703177 R.J.Browne, and B.L.Stitt (2005).
Active site occupancy required for catalytic cooperativity by Escherichia coli transcription termination factor Rho.
  J Biol Chem, 280, 13300-13303.  
15695817 S.Loverix, P.Geerlings, M.McNaughton, K.Augustyns, A.Vandemeulebroucke, J.Steyaert, and W.Versées (2005).
Substrate-assisted leaving group activation in enzyme-catalyzed N-glycosidic bond cleavage.
  J Biol Chem, 280, 14799-14802.  
14982926 W.Shi, L.M.Ting, G.A.Kicska, A.Lewandowicz, P.C.Tyler, G.B.Evans, R.H.Furneaux, K.Kim, S.C.Almo, and V.L.Schramm (2004).
Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function.
  J Biol Chem, 279, 18103-18106.
PDB codes: 1nw4 1q1g 1rr6
12842889 A.Lewandowicz, P.C.Tyler, G.B.Evans, R.H.Furneaux, and V.L.Schramm (2003).
Achieving the ultimate physiological goal in transition state analogue inhibitors for purine nucleoside phosphorylase.
  J Biol Chem, 278, 31465-31468.  
12704087 D.A.Kraut, K.S.Carroll, and D.Herschlag (2003).
Challenges in enzyme mechanism and energetics.
  Annu Rev Biochem, 72, 517-571.  
12937174 E.M.Bennett, C.Li, P.W.Allan, W.B.Parker, and S.E.Ealick (2003).
Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase.
  J Biol Chem, 278, 47110-47118.
PDB codes: 1pk7 1pk9 1pke 1pr0 1pr1 1pr2 1pr4 1pr5 1pr6 1pw7
12766151 J.A.McCann, and P.J.Berti (2003).
Adenine release is fast in MutY-catalyzed hydrolysis of G:A and 8-Oxo-G:A DNA mismatches.
  J Biol Chem, 278, 29587-29592.  
12496243 J.E.Lee, K.A.Cornell, M.K.Riscoe, and P.L.Howell (2003).
Structure of Escherichia coli 5'-methylthioadenosine/ S-adenosylhomocysteine nucleosidase inhibitor complexes provide insight into the conformational changes required for substrate binding and catalysis.
  J Biol Chem, 278, 8761-8770.
PDB codes: 1nc1 1nc3
14517232 K.Hövel, D.Shallom, K.Niefind, V.Belakhov, G.Shoham, T.Baasov, Y.Shoham, and D.Schomburg (2003).
Crystal structure and snapshots along the reaction pathway of a family 51 alpha-L-arabinofuranosidase.
  EMBO J, 22, 4922-4932.
PDB codes: 1pz2 1pz3 1qw8 1qw9
14580190 M.A.Bianchet, L.A.Seiple, Y.L.Jiang, Y.Ichikawa, L.M.Amzel, and J.T.Stivers (2003).
Electrostatic guidance of glycosyl cation migration along the reaction coordinate of uracil DNA glycosylase.
  Biochemistry, 42, 12455-12460.
PDB code: 1q3f
14522996 M.D.Jackson, M.T.Schmidt, N.J.Oppenheimer, and J.M.Denu (2003).
Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases.
  J Biol Chem, 278, 50985-50998.  
12947189 S.J.Benkovic, and S.Hammes-Schiffer (2003).
A perspective on enzyme catalysis.
  Science, 301, 1196-1202.  
12180982 G.Stoychev, B.Kierdaszuk, and D.Shugar (2002).
Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems.
  Eur J Biochem, 269, 4048-4057.  
12171925 W.Shi, A.E.Sarver, C.C.Wang, K.S.Tanaka, S.C.Almo, and V.L.Schramm (2002).
Closed site complexes of adenine phosphoribosyltransferase from Giardia lamblia reveal a mechanism of ribosyl migration.
  J Biol Chem, 277, 39981-39988.
PDB codes: 1l1q 1l1r
11578929 V.L.Schramm (2001).
Transition state variation in enzymatic reactions.
  Curr Opin Chem Biol, 5, 556-563.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.