PDBsum entry 1a4l

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
349 a.a. *
DCF ×4
_ZN ×4
Waters ×233
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Ada structure complexed with deoxycoformycin at ph 7.0
Structure: Adenosine deaminase. Chain: a, b, c, d. Synonym: ada. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.60Å     R-factor:   0.185     R-free:   0.272
Authors: Z.Wang,F.A.Quiocho
Key ref:
Z.Wang and F.A.Quiocho (1998). Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity. Biochemistry, 37, 8314-8324. PubMed id: 9622483 DOI: 10.1021/bi980324o
31-Jan-98     Release date:   14-Oct-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P03958  (ADA_MOUSE) -  Adenosine deaminase
352 a.a.
349 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Adenosine deaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Adenosine + H2O = inosine + NH3
+ H(2)O
Bound ligand (Het Group name = DCF)
matches with 90.00% similarity
+ NH(3)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   13 terms 
  Biological process     cell adhesion   50 terms 
  Biochemical function     hydrolase activity     6 terms  


    Added reference    
DOI no: 10.1021/bi980324o Biochemistry 37:8314-8324 (1998)
PubMed id: 9622483  
Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity.
Z.Wang, F.A.Quiocho.
Adenosine deaminase, which catalyzes the irreversible hydrolytic deamination of adenosine nucleosides to inosine nucleosides and ammonia, is a key enzyme in purine metabolism and lymphoid development. The X-ray structures of murine adenosine deaminase with bound potent inhibitors (Ki values approximately 10(-13) M) (8R)-hydroxyl-2'-deoxycoformycin (pentostatin), a transition state analogue, and (6S)-hydroxyl-1,6-dihydropurine riboside, a reaction coordinate analogue, have been determined and refined to resolutions of 2.6 and 1.95 A, respectively. Crystals of both complexes were obtained at pH 7, where the enzyme is fully active, in an identical space group with the asymmetric unit containing four molecules. In addition to the very high degree of similarity between the four independent molecules in each complex structure, there is also considerable structural similarity of the complex with the dihydropurine riboside with that of an identical complex previously determined at pH 4.2 where the enzyme is 20% active. The interactions between the enzyme and the two analogues are extremely similar. These include the coordination of the 8R- or 6S-hydroxyl group of the analogues to the Zn2+ which mainly contributes to the strong potency and very high degree of stereospecificity of inhibition by these analogues. The interactions are further indicative of the structural and chemical requirements of substrates. These structures and recent site-directed mutagenesis have further shed light on the catalytic mechanism of the enzyme.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19281183 D.F.Xiang, Y.Patskovsky, C.Xu, A.J.Meyer, J.M.Sauder, S.K.Burley, S.C.Almo, and F.M.Raushel (2009).
Functional identification of incorrectly annotated prolidases from the amidohydrolase superfamily of enzymes.
  Biochemistry, 48, 3730-3742.
PDB codes: 3be7 3dug
19274093 D.Y.Little, and L.Chen (2009).
Identification of coevolving residues and coevolution potentials emphasizing structure, bond formation and catalytic coordination in protein evolution.
  PLoS ONE, 4, e4762.  
19728741 M.C.Ho, M.B.Cassera, D.C.Madrid, L.M.Ting, P.C.Tyler, K.Kim, S.C.Almo, and V.L.Schramm (2009).
Structural and metabolic specificity of methylthiocoformycin for malarial adenosine deaminases.
  Biochemistry, 48, 9618-9626.
PDB codes: 3ewc 3ewd
19618900 O.R.Ludek, G.K.Schroeder, C.Liao, P.L.Russ, R.Wolfenden, and V.E.Marquez (2009).
Synthesis and conformational analysis of locked carbocyclic analogues of 1,3-diazepinone riboside, a high-affinity cytidine deaminase inhibitor.
  J Org Chem, 74, 6212-6223.  
20183605 V.E.Marquez, G.K.Schroeder, O.R.Ludek, M.A.Siddiqui, A.Ezzitouni, and R.Wolfenden (2009).
Contrasting behavior of conformationally locked carbocyclic nucleosides of adenosine and cytidine as substrates for deaminases.
  Nucleosides Nucleotides Nucleic Acids, 28, 614-632.  
18602399 E.T.Larson, W.Deng, B.E.Krumm, A.Napuli, N.Mueller, W.C.Van Voorhis, F.S.Buckner, E.Fan, A.Lauricella, G.DeTitta, J.Luft, F.Zucker, W.G.Hol, C.L.Verlinde, and E.A.Merritt (2008).
Structures of substrate- and inhibitor-bound adenosine deaminase from a human malaria parasite show a dramatic conformational change and shed light on drug selectivity.
  J Mol Biol, 381, 975-988.
PDB codes: 2pgf 2pgr 2qvn
17521911 G.Butora, D.B.Olsen, S.S.Carroll, D.R.McMasters, C.Schmitt, J.F.Leone, M.Stahlhut, C.Burlein, and M.Maccoss (2007).
Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine.
  Bioorg Med Chem, 15, 5219-5229.  
17517885 S.Escusa, D.Laporte, A.Massoni, H.Boucherie, A.Dautant, and B.Daignan-Fornier (2007).
Skp1-Cullin-F-box-dependent degradation of Aah1p requires its interaction with the F-box protein Saf1p.
  J Biol Chem, 282, 20097-20103.  
16543243 B.W.Han, C.A.Bingman, D.K.Mahnke, R.M.Bannen, S.Y.Bednarek, R.L.Sabina, and G.N.Phillips (2006).
Membrane association, mechanism of action, and structure of Arabidopsis embryonic factor 1 (FAC1).
  J Biol Chem, 281, 14939-14947.
PDB code: 2a3l
16963440 M.Goto, H.Hayashi, I.Miyahara, K.Hirotsu, M.Yoshida, and T.Oikawa (2006).
Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (gamma-resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005.
  J Biol Chem, 281, 34365-34373.
PDB codes: 2dvt 2dvu 2dvx
16245692 I.A.Il'icheva, I.u.P.Zarubin, P.A.Kostin, D.V.Mirgorodskiń≠, P.P.Purygin, and V.L.Florent'ev (2005).
[Theoretical study of the structure of adenosine deaminase complexes with adenosine analogues: I. Aza-, deaza- and isomeric azadeazaanalogues of adenosine]
  Bioorg Khim, 31, 488-502.  
15860561 K.Wang, and R.Samudrala (2005).
FSSA: a novel method for identifying functional signatures from structural alignments.
  Bioinformatics, 21, 2969-2977.  
16245011 S.A.Maier, J.R.Galellis, and H.E.McDermid (2005).
Phylogenetic analysis reveals a novel protein family closely related to adenosine deaminase.
  J Mol Evol, 61, 776-794.  
14557261 F.Vincent, D.Yates, E.Garman, G.J.Davies, and J.A.Brannigan (2004).
The three-dimensional structure of the N-acetylglucosamine-6-phosphate deacetylase, NagA, from Bacillus subtilis: a member of the urease superfamily.
  J Biol Chem, 279, 2809-2816.
PDB codes: 1un7 2vhl
14685275 R.C.Deo, E.F.Schmidt, A.Elhabazi, H.Togashi, S.K.Burley, and S.M.Strittmatter (2004).
Structural bases for CRMP function in plexin-dependent semaphorin3A signaling.
  EMBO J, 23, 9.
PDB code: 1kcx
12637534 T.P.Ko, J.J.Lin, C.Y.Hu, Y.H.Hsu, A.H.Wang, and S.H.Liaw (2003).
Crystal structure of yeast cytosine deaminase. Insights into enzyme mechanism and evolution.
  J Biol Chem, 278, 19111-19117.
PDB code: 1uaq
11223861 G.Cristalli, S.Costanzi, C.Lambertucci, G.Lupidi, S.Vittori, R.Volpini, and E.Camaioni (2001).
Adenosine deaminase: functional implications and different classes of inhibitors.
  Med Res Rev, 21, 105-128.  
11395407 J.A.Gerlt, and P.C.Babbitt (2001).
Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies.
  Annu Rev Biochem, 70, 209-246.  
10805768 D.K.Leung, Z.Yang, and R.Breslow (2000).
Selective disruption of protein aggregation by cyclodextrin dimers.
  Proc Natl Acad Sci U S A, 97, 5050-5053.  
10704207 H.Ford, F.Dai, L.Mu, M.A.Siddiqui, M.C.Nicklaus, L.Anderson, V.E.Marquez, and J.J.Barchi (2000).
Adenosine deaminase prefers a distinct sugar ring conformation for binding and catalysis: kinetic and structural studies.
  Biochemistry, 39, 2581-2592.  
10545376 U.Ryde (1999).
Carboxylate binding modes in zinc proteins: A theoretical study
  Biophys J, 77, 2777-2787.  
9914255 U.Ermler, W.Grabarse, S.Shima, M.Goubeaud, and R.K.Thauer (1998).
Active sites of transition-metal enzymes with a focus on nickel.
  Curr Opin Struct Biol, 8, 749-758.  
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.