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Hydrolase PDB id
1ctu
Jmol
Contents
Protein chain
294 a.a. *
Ligands
ZEB
Metals
_ZN
Waters ×48
* Residue conservation analysis
PDB id:
1ctu
Name: Hydrolase
Title: Transition-state selectivity for a single oh group during ca cytidine deaminase
Structure: Cytidine deaminase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.190    
Authors: S.Xiang,S.A.Short,R.Wolfenden,C.W.Carter
Key ref:
S.Xiang et al. (1995). Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase. Biochemistry, 34, 4516-4523. PubMed id: 7718553 DOI: 10.1021/bi00014a003
Date:
11-Feb-95     Release date:   08-May-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0ABF6  (CDD_ECOLI) -  Cytidine deaminase
Seq:
Struc: 		294 a.a.
294 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.5.4.5  - Cytidine deaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Cytidine + H2O = uridine + NH3
Cytidine
 + H(2)O
 =
uridine
Bound ligand (Het Group name = ZEB)
corresponds exactly 		+ NH(3)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytosol   1 term 
  Biological process     nucleobase, nucleoside and nucleotide interconversion   2 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi00014a003 Biochemistry 34:4516-4523 (1995)
PubMed id: 7718553  
 
 
Transition-state selectivity for a single hydroxyl group during catalysis by cytidine deaminase.
S.Xiang, S.A.Short, R.Wolfenden, C.W.Carter.
 
  ABSTRACT  
 
Cytidine deaminase binds transition-state analog inhibitors approximately 10(7) times more tightly than corresponding 3,4-dihydro analogs containing a proton in place of the 4-hydroxyl group. X-ray crystal structures of complexes with the two matched inhibitors differ only near a "trapped" water molecule in the complex with the 3,4-dihydro analog, where contacts are substantially less favorable than those with the hydroxyl group of the transition-state analog. The hydrogen bond between the hydroxyl group and the Glu 104 carboxylate shortens in that complex, and may become a "low-barrier" hydrogen bond, since at the same time the bond between zinc and the Cys 132 thiolate ligand lengthens. These differences must therefore account for most of the differential binding affinity related to catalysis. Moreover, the trapped water molecule retains some of the binding energy stabilizing the hydroxyl group in the transition-state analog complex. To this extent, the ratio of binding affinities for the two compounds is smaller than the true contribution of the hydroxyl group, a conclusion with significant bearing on interpreting difference free energies derived from substituent effects arising from chemical modification and/or mutagenesis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20116858 X.Li, S.A.Hayik, and K.M.Merz (2010).
QM/MM X-ray refinement of zinc metalloenzymes.
  J Inorg Biochem, 104, 512-522.  
19389408 E.Harjes, P.J.Gross, K.M.Chen, Y.Lu, K.Shindo, R.Nowarski, J.D.Gross, M.Kotler, R.S.Harris, and H.Matsuo (2009).
An extended structure of the APOBEC3G catalytic domain suggests a unique holoenzyme model.
  J Mol Biol, 389, 819-832.
PDB code: 2kem
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.  
18074341 A.D.Hill, and P.J.Reilly (2008).
A Gibbs free energy correlation for automated docking of carbohydrates.
  J Comput Chem, 29, 1131-1141.  
17622519 A.K.Singh, S.Mehtab, U.P.Singh, and V.Aggarwal (2007).
Tripodal chelating ligand-based sensor for selective determination of Zn(II) in biological and environmental samples.
  Anal Bioanal Chem, 388, 1867-1876.  
14516197 H.J.Tran, M.D.Allen, J.Löwe, and M.Bycroft (2003).
Structure of the Jab1/MPN domain and its implications for proteasome function.
  Biochemistry, 42, 11460-11465.
PDB code: 1oi0
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
14502542 T.X.Xiang, R.Niemi, P.Bummer, and B.D.Anderson (2003).
Epimer interconversion, isomerization, and hydrolysis of tetrahydrouridine: implications for cytidine deaminase inhibition.
  J Pharm Sci, 92, 2027-2039.  
14751833 V.E.Marquez, R.Eritja, J.A.Kelley, D.Vanbemmel, and J.K.Christman (2003).
Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (zebularine) at the GCGC recognition domain.
  Ann N Y Acad Sci, 1002, 154-164.  
11900535 M.J.Snider, D.Lazarevic, and R.Wolfenden (2002).
Catalysis by entropic effects: the action of cytidine deaminase on 5,6-dihydrocytidine.
  Biochemistry, 41, 3925-3930.  
12021441 R.C.Noonan, C.W.Carter CW, and C.K.Bagdassarian (2002).
Enzymatic conformational fluctuations along the reaction coordinate of cytidine deaminase.
  Protein Sci, 11, 1424-1434.  
11420434 K.O.Alper, M.Singla, J.L.Stone, and C.K.Bagdassarian (2001).
Correlated conformational fluctuations during enzymatic catalysis: Implications for catalytic rate enhancement.
  Protein Sci, 10, 1319-1330.  
9931020 R.L.D'Ordine, T.J.Klem, and V.J.Davisson (1999).
N1-(5'-phosphoribosyl)adenosine-5'-monophosphate cyclohydrolase: purification and characterization of a unique metalloenzyme.
  Biochemistry, 38, 1537-1546.  
9477944 D.C.Carlow, S.A.Short, and R.Wolfenden (1998).
Complementary truncations of a hydrogen bond to ribose involved in transition-state stabilization by cytidine deaminase.
  Biochemistry, 37, 1199-1203.  
9718310 D.Carlow, and R.Wolfenden (1998).
Substrate connectivity effects in the transition state for cytidine deaminase.
  Biochemistry, 37, 11873-11878.  
9689841 H.Kubinyi (1998).
[Molecular similarity. 1. Chemical structure and biological action]
  Pharm Unserer Zeit, 27, 92.  
9622483 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.
PDB codes: 1a4l 1a4m
9348662 C.L.Perrin, and J.B.Nielson (1997).
"Strong" hydrogen bonds in chemistry and biology.
  Annu Rev Phys Chem, 48, 511-544.  
9048544 C.M.Wilmot, J.M.Murray, G.Alton, M.R.Parsons, M.A.Convery, V.Blakeley, A.S.Corner, M.M.Palcic, P.F.Knowles, M.J.McPherson, and S.E.Phillips (1997).
Catalytic mechanism of the quinoenzyme amine oxidase from Escherichia coli: exploring the reductive half-reaction.
  Biochemistry, 36, 1608-1620.
PDB code: 1spu
  9195866 J.A.Gerlt, M.M.Kreevoy, W.Cleland, and P.A.Frey (1997).
Understanding enzymic catalysis: the importance of short, strong hydrogen bonds.
  Chem Biol, 4, 259-267.  
9405473 X.Zhao, J.Liu, D.S.Hsu, S.Zhao, J.S.Taylor, and A.Sancar (1997).
Reaction mechanism of (6-4) photolyase.
  J Biol Chem, 272, 32580-32590.  
  8807842 J.P.Guthrie (1996).
Short strong hydrogen bonds: can they explain enzymic catalysis?
  Chem Biol, 3, 163-170.  
8664259 P.Shih, and R.Wolfenden (1996).
Enzyme-substrate complexes of adenosine and cytidine deaminases: absence of accumulation of water adducts.
  Biochemistry, 35, 4697-4703.  
8634261 S.Xiang, S.A.Short, R.Wolfenden, and C.W.Carter (1996).
Cytidine deaminase complexed to 3-deazacytidine: a "valence buffer" in zinc enzyme catalysis.
  Biochemistry, 35, 1335-1341.
PDB code: 1aln
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 code is shown on the right.