spacer
spacer

PDBsum entry 1ptw
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
1ptw

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
334 a.a. *
Ligands
AMP ×4
Metals
_ZN ×8
Waters ×86
* Residue conservation analysis
PDB id:
1ptw
Name: Hydrolase
Title: The crystal structure of amp-bound pde4 suggests a mechanism for phosphodiesterase catalysis
Structure: Camp-specific phosphodiesterase pde4d2. Chain: a, b, c, d. Fragment: catalytic domain. Synonym: dpde3, pde43, pde4d2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pde4d2. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.30Å     R-factor:   0.229     R-free:   0.274
Authors: Q.Huai,J.Colicelli,H.Ke
Key ref:
Q.Huai et al. (2003). The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis. Biochemistry, 42, 13220-13226. PubMed id: 14609333 DOI: 10.1021/bi034653e
Date:
23-Jun-03     Release date:   11-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q08499  (PDE4D_HUMAN) -  3',5'-cyclic-AMP phosphodiesterase 4D from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		809 a.a.
334 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.4.53  - 3',5'-cyclic-AMP phosphodiesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3',5'-cyclic AMP + H2O = AMP + H+
3',5'-cyclic AMP
 + H2O
 =
AMP
Bound ligand (Het Group name = AMP)
corresponds exactly 		+ H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1021/bi034653e Biochemistry 42:13220-13226 (2003)
PubMed id: 14609333  
 
 
The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis.
Q.Huai, J.Colicelli, H.Ke.
 
  ABSTRACT  
 
Cyclic nucleotide phosphodiesterases (PDEs) regulate the intracellular concentrations of cyclic 3',5'-adenosine and guanosine monophosphates (cAMP and cGMP, respectively) by hydrolyzing them to AMP and GMP, respectively. Family-selective inhibitors of PDEs have been studied for treatment of various human diseases. However, the catalytic mechanism of cyclic nucleotide hydrolysis by PDEs has remained unclear. We determined the crystal structure of the human PDE4D2 catalytic domain in complex with AMP at 2.4 A resolution. In this structure, two divalent metal ions simultaneously interact with the phosphate group of AMP, implying a binuclear catalysis. In addition, the structure suggested that a hydroxide ion or a water bridging two metal ions may serve as the nucleophile for the hydrolysis of the cAMP phosphodiester bond.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20121115 H.Wang, X.Luo, M.Ye, J.Hou, H.Robinson, and H.Ke (2010).
Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis.
  J Med Chem, 53, 1726-1731.
PDB codes: 3k3e 3k3h
19464886 A.P.Skoumbourdis, C.A.Leclair, E.Stefan, A.G.Turjanski, W.Maguire, S.A.Titus, R.Huang, D.S.Auld, J.Inglese, C.P.Austin, S.W.Michnick, M.Xia, and C.J.Thomas (2009).
Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors.
  Bioorg Med Chem Lett, 19, 3686-3692.  
19641165 J.L.Weeks, J.D.Corbin, and S.H.Francis (2009).
Interactions between cyclic nucleotide phosphodiesterase 11 catalytic site and substrates or tadalafil and role of a critical Gln-869 hydrogen bond.
  J Pharmacol Exp Ther, 331, 133-141.  
19828435 J.Pandit, M.D.Forman, K.F.Fennell, K.S.Dillman, and F.S.Menniti (2009).
Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct.
  Proc Natl Acad Sci U S A, 106, 18225-18230.
PDB codes: 3ibj 3itm 3itu
19438719 R.Mega, N.Kondo, N.Nakagawa, S.Kuramitsu, and R.Masui (2009).
Two dNTP triphosphohydrolases from Pseudomonas aeruginosa possess diverse substrate specificities.
  FEBS J, 276, 3211-3221.  
18984055 Z.Yan, H.Wang, J.Cai, and H.Ke (2009).
Refolding and kinetic characterization of the phosphodiesterase-8A catalytic domain.
  Protein Expr Purif, 64, 82-88.  
17989916 N.Kondo, T.Nishikubo, T.Wakamatsu, H.Ishikawa, N.Nakagawa, S.Kuramitsu, and R.Masui (2008).
Insights into different dependence of dNTP triphosphohydrolase on metal ion species from intracellular ion concentrations in Thermus thermophilus.
  Extremophiles, 12, 217-223.  
18757755 S.Liu, M.N.Mansour, K.S.Dillman, J.R.Perez, D.E.Danley, P.A.Aeed, S.P.Simons, P.K.Lemotte, and F.S.Menniti (2008).
Structural basis for the catalytic mechanism of human phosphodiesterase 9.
  Proc Natl Acad Sci U S A, 105, 13309-13314.
PDB codes: 3dy8 3dyl 3dyn 3dyq 3dys
17582435 H.Wang, H.Robinson, and H.Ke (2007).
The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10.
  J Mol Biol, 371, 302-307.
PDB code: 2pw3
17389385 H.Wang, Y.Liu, J.Hou, M.Zheng, H.Robinson, and H.Ke (2007).
Structural insight into substrate specificity of phosphodiesterase 10.
  Proc Natl Acad Sci U S A, 104, 5782-5787.
PDB codes: 2oun 2oup 2ouq 2our 2ous 2ouu 2ouv 2ouy
17376027 M.Conti, and J.Beavo (2007).
Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling.
  Annu Rev Biochem, 76, 481-511.  
17242516 N.Kondo, N.Nakagawa, A.Ebihara, L.Chen, Z.J.Liu, B.C.Wang, S.Yokoyama, S.Kuramitsu, and R.Masui (2007).
Structure of dNTP-inducible dNTP triphosphohydrolase: insight into broad specificity for dNTPs and triphosphohydrolase-type hydrolysis.
  Acta Crystallogr D Biol Crystallogr, 63, 230-239.
PDB code: 2dqb
16102838 C.Lugnier (2006).
Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents.
  Pharmacol Ther, 109, 366-398.  
16735511 H.Wang, Y.Liu, Q.Huai, J.Cai, R.Zoraghi, S.H.Francis, J.D.Corbin, H.Robinson, Z.Xin, G.Lin, and H.Ke (2006).
Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development.
  J Biol Chem, 281, 21469-21479.
PDB codes: 2h40 2h42 2h44
16905100 J.Alvarado, A.Ghosh, T.Janovitz, A.Jauregui, M.S.Hasson, and D.A.Sanders (2006).
Origin of exopolyphosphatase processivity: Fusion of an ASKHA phosphotransferase and a cyclic nucleotide phosphodiesterase homolog.
  Structure, 14, 1263-1272.
PDB code: 1u6z
16539372 Q.Huai, Y.Sun, H.Wang, D.Macdonald, R.Aspiotis, H.Robinson, Z.Huang, and H.Ke (2006).
Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase.
  J Med Chem, 49, 1867-1873.
PDB codes: 2fm0 2fm5
16407275 R.Zoraghi, J.D.Corbin, and S.H.Francis (2006).
Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil affinity: its orientation impacts cGMP but not cAMP affinity.
  J Biol Chem, 281, 5553-5558.  
16460808 V.V.Gurevich, and E.V.Gurevich (2006).
The structural basis of arrestin-mediated regulation of G-protein-coupled receptors.
  Pharmacol Ther, 110, 465-502.  
  16966475 Z.Zhou, X.Wang, H.Y.Liu, X.Zou, M.Li, and T.C.Hwang (2006).
The two ATP binding sites of cystic fibrosis transmembrane conductance regulator (CFTR) play distinct roles in gating kinetics and energetics.
  J Gen Physiol, 128, 413-422.  
15994308 H.Wang, Y.Liu, Y.Chen, H.Robinson, and H.Ke (2005).
Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide phosphodiesterases 4 and 7.
  J Biol Chem, 280, 30949-30955.
PDB code: 1zkl
15870731 J.A.Doudna, and J.R.Lorsch (2005).
Ribozyme catalysis: not different, just worse.
  Nat Struct Mol Biol, 12, 395-402.  
16300476 K.Y.Zhang, P.N.Ibrahim, S.Gillette, and G.Bollag (2005).
Phosphodiesterase-4 as a potential drug target.
  Expert Opin Ther Targets, 9, 1283-1305.  
16223764 Z.Zhou, X.Wang, M.Li, Y.Sohma, X.Zou, and T.C.Hwang (2005).
High affinity ATP/ADP analogues as new tools for studying CFTR gating.
  J Physiol, 569, 447-457.  
15576036 G.L.Card, B.P.England, Y.Suzuki, D.Fong, B.Powell, B.Lee, C.Luu, M.Tabrizizad, S.Gillette, P.N.Ibrahim, D.R.Artis, G.Bollag, M.V.Milburn, S.H.Kim, J.Schlessinger, and K.Y.Zhang (2004).
Structural basis for the activity of drugs that inhibit phosphodiesterases.
  Structure, 12, 2233-2247.
PDB codes: 1xlx 1xlz 1xm4 1xm6 1xmu 1xmy 1xn0 1xom 1xon 1xoq 1xor 1xos 1xot 1xoz 1xp0
15260978 K.Y.Zhang, G.L.Card, Y.Suzuki, D.R.Artis, D.Fong, S.Gillette, D.Hsieh, J.Neiman, B.L.West, C.Zhang, M.V.Milburn, S.H.Kim, J.Schlessinger, and G.Bollag (2004).
A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases.
  Mol Cell, 15, 279-286.
PDB codes: 1t9r 1t9s 1taz 1tb5 1tb7 1tbb 1tbf
15210993 Q.Huai, H.Wang, W.Zhang, R.W.Colman, H.Robinson, and H.Ke (2004).
Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding.
  Proc Natl Acad Sci U S A, 101, 9624-9629.
PDB codes: 1tbm 2hd1
15378407 Y.Adachi, J.Yoshida, Y.Kodera, A.Kato, Y.Yoshikawa, Y.Kojima, and H.Sakurai (2004).
A new insulin-mimetic bis(allixinato)zinc(II) complex: structure-activity relationship of zinc(II) complexes.
  J Biol Inorg Chem, 9, 885-893.  
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.

 

spacer
spacer