PDBsum entry 1cg6

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Transferase PDB id
Jmol PyMol
Protein chain
268 a.a. *
Waters ×153
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of human 5'-deoxy-5'-methylthioadenosine phosphory complexed with 5'-deoxy-5'-methylthioadenosine and sulfate resolution
Structure: Protein (5'-deoxy-5'-methylthioadenosine phosphor chain: a. Synonym: mta phosphorylase, mtap. Engineered: yes. Mutation: yes. Other_details: complexed with 5'-deoxy-5'-methylthioadenosi sulfate
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: placenta. Cellular_location: cytoplasm. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Other_details: mtap cdna was isolated from a human placenta library and expressed in e. Coli
Biol. unit: Trimer (from PDB file)
1.70Å     R-factor:   0.202     R-free:   0.225
Authors: T.C.Appleby,M.D.Erion,S.E.Ealick
Key ref:
T.C.Appleby et al. (1999). The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis. Structure, 7, 629-641. PubMed id: 10404592 DOI: 10.1016/S0969-2126(99)80084-7
27-Mar-99     Release date:   05-Jul-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q13126  (MTAP_HUMAN) -  S-methyl-5'-thioadenosine phosphorylase
283 a.a.
268 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - S-methyl-5'-thioadenosine phosphorylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-methyl-5'-thioadenosine + phosphate = adenine + S-methyl-5-thio-alpha- D-ribose 1-phosphate
Bound ligand (Het Group name = MTA)
corresponds exactly
+ phosphate
= adenine
+ S-methyl-5-thio-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   4 terms 
  Biological process     nucleobase-containing compound metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1016/S0969-2126(99)80084-7 Structure 7:629-641 (1999)
PubMed id: 10404592  
The structure of human 5'-deoxy-5'-methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis.
T.C.Appleby, M.D.Erion, S.E.Ealick.
BACKGROUND: 5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAP) catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MTA) to adenine and 5-methylthio-D-ribose-1-phosphate. MTA is a by-product of polyamine biosynthesis, which is essential for cell growth and proliferation. This salvage reaction is the principle source of free adenine in human cells. Because of its importance in coupling the purine salvage pathway to polyamine biosynthesis MTAP is a potential chemotherapeutic target. RESULTS: We have determined the crystal structure of MTAP at 1.7 A resolution using multiwavelength anomalous diffraction phasing techniques. MTAP is a trimer comprised of three identical subunits. Each subunit consists of a single alpha/beta domain containing a central eight-stranded mixed beta sheet, a smaller five-stranded mixed beta sheet and six alpha helices. The native structure revealed the presence of an adenine molecule in the purine-binding site. The structure of MTAP with methylthioadenosine and sulfate ion soaked into the active site was also determined using diffraction data to 1.7 A resolution. CONCLUSIONS: The overall quaternary structure and subunit topology of MTAP are similar to mammalian purine nucleoside phosphorylase (PNP). The structures of the MTAP-ligand complexes provide a map of the active site and suggest possible roles for specific residues in substrate binding and catalysis. Residues accounting for the differences in substrate specificity between MTAP and PNP are also identified. Detailed information about the structure and chemical nature of the MTAP active site will aid in the rational design of inhibitors of this potential chemotherapeutic target. The MTAP structure represents the first structure of a mammalian PNP that is specific for 6-aminopurines.
  Selected figure(s)  
Figure 3.
Figure 3. Stereoview of the MTAP trimer. The trimer is viewed down the molecular/crystallographic threefold axis. Each subunit is shown in a different color, with MTA and sulfate modeled in red in each of the three active sites. Broken lines indicate residues 225–229, which are missing in the final model. (The figure was produced using the program MOLSCRIPT [41].)
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 629-641) copyright 1999.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20364833 D.Paul, S.E.O'Leary, K.Rajashankar, W.Bu, A.Toms, E.C.Settembre, J.M.Sanders, T.P.Begley, and S.E.Ealick (2010).
Glycal formation in crystals of uridine phosphorylase.
  Biochemistry, 49, 3499-3509.
PDB codes: 3ku4 3kuk 3kvr 3kvv 3kvy
20954236 D.R.Ronning, N.M.Iacopelli, and V.Mishra (2010).
Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.
  Protein Sci, 19, 2498-2510.
PDB codes: 3nm4 3nm5 3nm6
20693694 H.Xu (2010).
Enhancing MAD F(A) data for substructure determination.
  Acta Crystallogr D Biol Crystallogr, 66, 945-949.  
19740110 G.Cacciapuoti, I.Peluso, F.Fuccio, and M.Porcelli (2009).
Purine nucleoside phosphorylases from hyperthermophilic Archaea require a CXC motif for stability and folding.
  FEBS J, 276, 5799-5805.  
18219117 H.Xu, and C.M.Weeks (2008).
Rapid and automated substructure solution by Shake-and-Bake.
  Acta Crystallogr D Biol Crystallogr, 64, 172-177.  
17419725 G.Cacciapuoti, S.Gorassini, M.F.Mazzeo, R.A.Siciliano, V.Carbone, V.Zappia, and M.Porcelli (2007).
Biochemical and structural characterization of mammalian-like purine nucleoside phosphorylase from the Archaeon Pyrococcus furiosus.
  FEBS J, 274, 2482-2495.  
17521420 J.L.Jiménez, B.Hegemann, J.R.Hutchins, J.M.Peters, and R.Durbin (2007).
A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database.
  Genome Biol, 8, R90.  
17090056 V.Singh, and V.L.Schramm (2006).
Transition-state structure of human 5'-methylthioadenosine phosphorylase.
  J Am Chem Soc, 128, 14691-14696.  
15819883 G.Cacciapuoti, S.Forte, M.A.Moretti, A.Brio, V.Zappia, and M.Porcelli (2005).
A novel hyperthermostable 5'-deoxy-5'-methylthioadenosine phosphorylase from the archaeon Sulfolobus solfataricus.
  FEBS J, 272, 1886-1899.  
15983421 H.Xu, C.M.Weeks, and H.A.Hauptman (2005).
Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
  Acta Crystallogr D Biol Crystallogr, 61, 976-981.  
15746096 J.E.Lee, V.Singh, G.B.Evans, P.C.Tyler, R.H.Furneaux, K.A.Cornell, M.K.Riscoe, V.L.Schramm, and P.L.Howell (2005).
Structural rationale for the affinity of pico- and femtomolar transition state analogues of Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase.
  J Biol Chem, 280, 18274-18282.
PDB codes: 1y6q 1y6r
15983408 W.Bu, E.C.Settembre, M.H.el Kouni, and S.E.Ealick (2005).
Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines.
  Acta Crystallogr D Biol Crystallogr, 61, 863-872.
PDB codes: 1u1c 1u1d 1u1e 1u1f 1u1g
15817485 Y.Zang, W.H.Wang, S.W.Wu, S.E.Ealick, and C.C.Wang (2005).
Identification of a subversive substrate of Trichomonas vaginalis purine nucleoside phosphorylase and the crystal structure of the enzyme-substrate complex.
  J Biol Chem, 280, 22318-22325.
PDB codes: 1z33 1z34 1z35 1z36 1z37 1z38 1z39
15606771 G.Cacciapuoti, M.A.Moretti, S.Forte, A.Brio, L.Camardella, V.Zappia, and M.Porcelli (2004).
Methylthioadenosine phosphorylase from the archaeon Pyrococcus furiosus. Mechanism of the reaction and assignment of disulfide bonds.
  Eur J Biochem, 271, 4834-4844.  
15296732 Y.Zhang, S.E.Cottet, and S.E.Ealick (2004).
Structure of Escherichia coli AMP nucleosidase reveals similarity to nucleoside phosphorylases.
  Structure, 12, 1383-1394.
PDB codes: 1t8r 1t8s 1t8w 1t8y
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
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
12824877 Y.Kadariya, J.Nishioka, A.Nakamura, K.Kato-Nakazawa, and T.Nobori (2003).
Molecular characterization of 5'-deoxy-5'-methylthioadenosine phosphorylase-deficient mutant clones of murine lymphoma cell line R1.1.
  Cancer Sci, 94, 519-522.  
11847292 J.Pei, and N.V.Grishin (2002).
Breaking the singleton of germination protease.
  Protein Sci, 11, 691-697.  
11489901 T.C.Appleby, I.I.Mathews, M.Porcelli, G.Cacciapuoti, and S.E.Ealick (2001).
Three-dimensional structure of a hyperthermophilic 5'-deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus.
  J Biol Chem, 276, 39232-39242.
PDB codes: 1jds 1jdt 1jdu 1jdv 1jdz 1je0 1je1 1jp7 1jpv
11337031 A.Bzowska, E.Kulikowska, and D.Shugar (2000).
Purine nucleoside phosphorylases: properties, functions, and clinical aspects.
  Pharmacol Ther, 88, 349-425.  
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.