S H Francis

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. ncbi request reprint Isolated regulatory domains of cGMP-dependent protein kinase Ialpha and Ibeta retain dimerization and native cGMP-binding properties and undergo isoform-specific conformational changes
    Robyn Richie-Jannetta
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    J Biol Chem 281:6977-84. 2006
  2. pmc cGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake
    Jennifer A Steiner
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Brain 2:26. 2009
  3. ncbi request reprint Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Handb Exp Pharmacol 200:93-133. 2011
  4. pmc cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 2215 Garland Avenue, Nashville, TN 37232 0615, USA
    Pharmacol Rev 62:525-63. 2010
  5. ncbi request reprint Phosphodiesterase 11 (PDE11): is it a player in human testicular function?
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Int J Impot Res 17:467-8. 2005
  6. doi request reprint Molecular mechanisms that could contribute to prolonged effectiveness of PDE5 inhibitors to improve erectile function
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Int J Impot Res 20:333-42. 2008
  7. ncbi request reprint Single step isolation of sildenafil from commercially available Viagra tablets
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Int J Impot Res 15:369-72. 2003
  8. ncbi request reprint Sildenafil: efficacy, safety, tolerability and mechanism of action in treating erectile dysfunction
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Light Hall Room 702, Nashville, TN 37232 0615, USA
    Expert Opin Drug Metab Toxicol 1:283-93. 2005
  9. ncbi request reprint Molecular properties of mammalian proteins that interact with cGMP: protein kinases, cation channels, phosphodiesterases, and multi-drug anion transporters
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Front Biosci 10:2097-117. 2005
  10. ncbi request reprint Phosphodiesterase-5 inhibition: the molecular biology of erectile function and dysfunction
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Light Hall, Room 702, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Urol Clin North Am 32:419-29, vi. 2005

Collaborators

  • Mitsi A Blount
  • J D Corbin
  • Jennifer L Busch
  • Hengming Ke
  • Yasmin Shakur
  • Jill Trewhella
  • James H Hurley
  • Andrea Johner
  • L Liu
  • Stefan Kunz
  • M E Wall
  • Sunil Laxman
  • Roya Zoraghi
  • Emmanuel P Bessay
  • Huanchen Wang
  • James L Weeks
  • Kennard A Grimes
  • Robyn Richie-Jannetta
  • Jun Kotera
  • Alfreda Beasley
  • Qing Huai
  • Jennifer A Steiner
  • Howard Robinson
  • Randy D Blakely
  • I V Turko
  • Yudong Liu
  • J L Weeks
  • Chong Bin Zhu
  • L M McAllister-Lucas
  • V K Gopal
  • Jane Wright
  • Carrie C Buchanan
  • Ana Marin D Carneiro
  • Wolfgang R Dostmann
  • Christian K Nicki
  • Heinrich J G Matthies
  • Harish C Prasad
  • Mengchun Ye
  • Guiting Lin
  • Jiwen Cai
  • Kristin A Higgins
  • Zhongcheng Xin
  • K R Sekhar
  • Melissa K Thomas
  • Konjeti Raja Sekhar
  • R Zoraghi
  • A Beasley
  • Alfreda Rouse
  • William A Hewlett
  • C E Poteet-Smith
  • T L Haik
  • W K Sonnenburg
  • D Seger
  • J L Colbran
  • J B Shabb
  • F Burns
  • J A Beavo
  • M K Thomas
  • H L Trong
  • K A Walsh
  • A Kadlecek
  • L Wolfe

Detail Information

Publications54

  1. ncbi request reprint Isolated regulatory domains of cGMP-dependent protein kinase Ialpha and Ibeta retain dimerization and native cGMP-binding properties and undergo isoform-specific conformational changes
    Robyn Richie-Jannetta
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    J Biol Chem 281:6977-84. 2006
    ..The cGMP-induced conformational changes in the respective R domains are likely to be critical for kinase activation...
  2. pmc cGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake
    Jennifer A Steiner
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Brain 2:26. 2009
    ..PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear...
  3. ncbi request reprint Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Handb Exp Pharmacol 200:93-133. 2011
    ..Related compounds target other PDEs and show therapeutic promise for a number of maladies...
  4. pmc cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 2215 Garland Avenue, Nashville, TN 37232 0615, USA
    Pharmacol Rev 62:525-63. 2010
    ..Potential for use of these medications in the treatment of other maladies continues to emerge...
  5. ncbi request reprint Phosphodiesterase 11 (PDE11): is it a player in human testicular function?
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Int J Impot Res 17:467-8. 2005
    ..In this perspective, Sharron Francis, a noted PDE expert, and a co-author of one of the recent papers mentioned above, sheds further light on this contested topic...
  6. doi request reprint Molecular mechanisms that could contribute to prolonged effectiveness of PDE5 inhibitors to improve erectile function
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Int J Impot Res 20:333-42. 2008
    ....
  7. ncbi request reprint Single step isolation of sildenafil from commercially available Viagra tablets
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Int J Impot Res 15:369-72. 2003
    ..This protocol and similar procedures will allow investigators to easily isolate sufficient amounts of sildenafil or other PDE5 inhibitors for conducting biochemical and in vitro studies of drug action...
  8. ncbi request reprint Sildenafil: efficacy, safety, tolerability and mechanism of action in treating erectile dysfunction
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Light Hall Room 702, Nashville, TN 37232 0615, USA
    Expert Opin Drug Metab Toxicol 1:283-93. 2005
    ....
  9. ncbi request reprint Molecular properties of mammalian proteins that interact with cGMP: protein kinases, cation channels, phosphodiesterases, and multi-drug anion transporters
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Front Biosci 10:2097-117. 2005
    ....
  10. ncbi request reprint Phosphodiesterase-5 inhibition: the molecular biology of erectile function and dysfunction
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Light Hall, Room 702, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Urol Clin North Am 32:419-29, vi. 2005
    ..By exploiting features of PDE-5 regulatory mechanisms that modulate PDE-5 function, the inhibitors enhance their own potencies...
  11. doi request reprint Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Physiol Rev 91:651-90. 2011
    ..The many recent advances in understanding PDE structures, functions, and physiological actions are discussed in this review...
  12. doi request reprint PDE5 inhibitors: targeting erectile dysfunction in diabetics
    Sharron H Francis
    Department Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, United States
    Curr Opin Pharmacol 11:683-8. 2011
    ..Use of PDE5 inhibitors in pre-diabetic and diabetic men may protect cardiovascular health, including vascular function in penile tissues...
  13. ncbi request reprint High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients
    J L Weeks
    Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232 0615, USA
    Int J Impot Res 17:5-9. 2005
    ..PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients...
  14. ncbi request reprint The structure of a bovine lung cGMP-binding, cGMP-specific phosphodiesterase deduced from a cDNA clone
    L M McAllister-Lucas
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615
    J Biol Chem 268:22863-73. 1993
    ..The amino-terminal 142 residues of cGB-PDE showed no significant homology to other PDEs and contained the serine (AA 92) which is phosphorylated by cGMP-dependent protein kinase...
  15. ncbi request reprint Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities
    J D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Eur J Biochem 267:2760-7. 2000
    ..13 to 0.03 microM. The mechanism by which phosphorylation of PDE5 by PKG could be involved in physiological negative-feedback regulation of cGMP levels is discussed...
  16. ncbi request reprint A photoaffinity probe covalently modifies the catalytic site of the cGMP-binding cGMP-specific phosphodiesterase (PDE-5)
    J D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Cell Biochem Biophys 29:145-57. 1998
    ..It is concluded that the interaction of this photoaffinity probe with PDE-5 is highly specific for the catalytic site over the allosteric binding sites of PDE-5 and could prove useful in studies to map the catalytic site of PDE-5...
  17. ncbi request reprint An essential aspartic acid at each of two allosteric cGMP-binding sites of a cGMP-specific phosphodiesterase
    L M McAllister-Lucas
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0165, USA
    J Biol Chem 270:30671-9. 1995
    ....
  18. ncbi request reprint Identification of key amino acids in a conserved cGMP-binding site of cGMP-binding phosphodiesterases. A putative NKXnD motif for cGMP binding
    I V Turko
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Biol Chem 271:22240-4. 1996
    ..This suggested that cGMP binding to site a does not influence the catalytic properties of cGB-PDE...
  19. pmc Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation
    I V Turko
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Biochem J 329:505-10. 1998
    ..It is concluded that cGMP binding to the allosteric sites of cGB-PDE does not directly affect catalysis, but binding to both of these sites regulates phosphorylation of this enzyme...
  20. ncbi request reprint Allosteric sites of phosphodiesterase-5 (PDE5). A potential role in negative feedback regulation of cGMP signaling in corpus cavernosum
    V K Gopal
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA
    Eur J Biochem 268:3304-12. 2001
    ..This introduces a new concept for cyclic nucleotide signaling...
  21. ncbi request reprint Histidine-607 and histidine-643 provide important interactions for metal support of catalysis in phosphodiesterase-5
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Biochemistry 39:9591-6. 2000
    ....
  22. ncbi request reprint Pharmacology of phosphodiesterase-5 inhibitors
    J D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Int J Clin Pract 56:453-9. 2002
    ..Each PDE5 inhibitor has a distinct selectivity that contributes to its safety profile. As with all new drugs, and especially those in a new class, careful evaluation will be necessary to ensure the optimal use of the PDE5 inhibitors...
  23. ncbi request reprint Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase
    S H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615
    J Biol Chem 269:22477-80. 1994
    ....
  24. ncbi request reprint Properties of a cGMP-dependent monomeric protein kinase from bovine aorta
    L Wolfe
    Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232
    J Biol Chem 264:4157-62. 1989
    ..The results indicated that the catalytic domain, cGMP binding domain(s), and inhibitory domain of cGK interact primarily within the same subunit rather than between subunits of the dimer as previously hypothesized for dimeric cGK...
  25. ncbi request reprint Identification of critical determinants for autoinhibition in the pseudosubstrate region of type I alpha cAMP-dependent protein kinase
    C E Poteet-Smith
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Biol Chem 272:379-88. 1997
    ..The inhibitory potency of RI subunit was unchanged when Glu101 was replaced with Ala or Gln. It is concluded that Arg94, Arg95 and, to a lesser extent, Ile98 are vital constituents of PKA autoinhibition by type I alpha R subunit...
  26. ncbi request reprint Substrate- and kinase-directed regulation of phosphorylation of a cGMP-binding phosphodiesterase by cGMP
    M K Thomas
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615
    J Biol Chem 265:14971-8. 1990
    ..Such regulation would greatly increase the selectivity of the phosphorylation of cG-BPDE and would represent a unique mechanism of action of a cyclic nucleotide or other second messenger...
  27. ncbi request reprint N-Terminal domain of phosphodiesterase-11A4 (PDE11A4) decreases affinity of the catalytic site for substrates and tadalafil, and is involved in oligomerization
    James L Weeks
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, Tennessee 37232 0615, USA
    Biochemistry 46:10353-64. 2007
    ....
  28. ncbi request reprint A 46-amino acid segment in phosphodiesterase-5 GAF-B domain provides for high vardenafil potency over sildenafil and tadalafil and is involved in phosphodiesterase-5 dimerization
    Mitsi A Blount
    Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Mol Pharmacol 70:1822-31. 2006
    ..This is the first evidence that PDE5 R domain, and GAF-B in particular, influences affinity and selectivity of the catalytic site for certain classes of inhibitors...
  29. ncbi request reprint Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil affinity: its orientation impacts cGMP but not cAMP affinity
    Roya Zoraghi
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    J Biol Chem 281:5553-8. 2006
    ....
  30. doi request reprint Phosphorylation increases affinity of the phosphodiesterase-5 catalytic site for tadalafil
    Emmanuel P Bessay
    Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    J Pharmacol Exp Ther 325:62-8. 2008
    ..By increasing the affinity of the catalytic site, phosphorylation should also consequently increase the potency and duration of PDE5 inhibitor action...
  31. ncbi request reprint Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development
    Huanchen Wang
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, 27599 7260, USA
    J Biol Chem 281:21469-79. 2006
    ....
  32. ncbi request reprint Critical amino acids in phosphodiesterase-5 catalytic site that provide for high-affinity interaction with cyclic guanosine monophosphate and inhibitors
    Roya Zoraghi
    Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Biochemistry 46:13554-63. 2007
    ....
  33. ncbi request reprint Phosphorylation of phosphodiesterase-5 is promoted by a conformational change induced by sildenafil, vardenafil, or tadalafil
    Emmanuel P Bessay
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Front Biosci 12:1899-910. 2007
    ....
  34. ncbi request reprint Conversion of phosphodiesterase-5 (PDE5) catalytic site to higher affinity by PDE5 inhibitors
    Mitsi A Blount
    Department of Molecular Physiology and Biophysics, Light Hall Room 702, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    J Pharmacol Exp Ther 323:730-7. 2007
    ..This effect is predicted to improve the substrate affinity or inhibitory potencies of these compounds in intact cells...
  35. pmc Conformational variations of both phosphodiesterase-5 and inhibitors provide the structural basis for the physiological effects of vardenafil and sildenafil
    Huanchen Wang
    Department of Biochemistry and Biophysics, The University of North Carolina, Chapel Hill, NC 27599 7260, USA
    Mol Pharmacol 73:104-10. 2008
    ..The conformational variation of both PDE5 and the inhibitors provides structural insight into the different potencies of the drugs...
  36. ncbi request reprint Mechanisms of autoinhibition in cyclic nucleotide-dependent protein kinases
    Sharron H Francis
    Dept of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Front Biosci 7:d580-92. 2002
    ..Thus, capacity for autoinhibition of PKA or PKG is provided by contacts involving direct interactions with the catalytic site and by contacts that stabilize an inactive conformation...
  37. ncbi request reprint A conserved serine juxtaposed to the pseudosubstrate site of type I cGMP-dependent protein kinase contributes strongly to autoinhibition and lower cGMP affinity
    Jennifer L Busch
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    J Biol Chem 277:34048-54. 2002
    ..The combined results demonstrate that a conserved serine juxtaposed to the pseudosubstrate site in type I PKGs contributes importantly to enzyme function by increasing autoinhibition and decreasing cGMP binding affinity...
  38. ncbi request reprint Phosphorylation of isolated human phosphodiesterase-5 regulatory domain induces an apparent conformational change and increases cGMP binding affinity
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Biol Chem 277:47581-7. 2002
    ..Conformational change(s) elicited by phosphorylation of the R domain within the PDE5 holoenzyme may also cause or participate in stimulating catalysis...
  39. ncbi request reprint Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    Urology 60:4-11. 2002
    ..Selective inhibition of PDE5 is a rational therapeutic approach in ED, as proved by the clinical success of sildenafil...
  40. pmc Mechanisms associated with cGMP binding and activation of cGMP-dependent protein kinase
    Michael E Wall
    Computer and Computational Sciences and Bioscience Divisions, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
    Proc Natl Acad Sci U S A 100:2380-5. 2003
    ....
  41. pmc cGMP-dependent protein kinase protects cGMP from hydrolysis by phosphodiesterase-5
    Jun Kotera
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Biochem J 372:419-26. 2003
    ....
  42. ncbi request reprint [3H]sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous, and stimulated by cGMP
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, TN 37232 0615, USA
    Mol Pharmacol 63:1364-72. 2003
    ..The data also indicate that after physiological elevation, cGMP may directly stimulate the catalytic site by binding to the allosteric cGMP-binding sites of PDE5, thus causing negative feedback on this pathway...
  43. ncbi request reprint Dimerization of cGMP-dependent protein kinase Ibeta is mediated by an extensive amino-terminal leucine zipper motif, and dimerization modulates enzyme function
    Robyn Richie-Jannetta
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Biol Chem 278:50070-9. 2003
    ..These results indicate that dimerization increases sensitivity for cGMP activation of the enzyme...
  44. ncbi request reprint Molecular mechanisms and pharmacokinetics of phosphodiesterase-5 antagonists
    Sharron H Francis
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Light Hall Room 702, Nashville, TN 37232 0615, USA
    Curr Urol Rep 4:457-65. 2003
    ....
  45. ncbi request reprint Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity
    Qing Huai
    Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599 7260, USA
    J Biol Chem 279:13095-101. 2004
    ..IBMX binds to a subpocket that comprises key residues Ile-336, Phe-340, Gln-369, and Phe-372 of PDE4D2 or Val-782, Phe-786, Gln-817, and Phe-820 of PDE5A1. This subpocket may be a common site for binding nonselective inhibitors of PDEs...
  46. ncbi request reprint High lung PDE5: a strong basis for treating pulmonary hypertension with PDE5 inhibitors
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Biochem Biophys Res Commun 334:930-8. 2005
    ..The PDE5 level was one-half that of PKG in heart. Thus, abundance of PDE5 in lung vascular smooth muscle provides a strong molecular basis for PDE5 inhibitor treatment of pulmonary hypertension...
  47. ncbi request reprint Radiolabeled ligand binding to the catalytic or allosteric sites of PDE5 and PDE11
    James L Weeks
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
    Methods Mol Biol 307:239-62. 2005
    ..These techniques have also been successfully applied to the study of binding of radiolabeled PDE5 inhibitors to PDE11, suggesting that these methods are applicable to the study of other PDEs, and perhaps other enzyme families...
  48. ncbi request reprint Structural and functional features in human PDE5A1 regulatory domain that provide for allosteric cGMP binding, dimerization, and regulation
    Roya Zoraghi
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Biol Chem 280:12051-63. 2005
    ..Results yield new insights into PDE5 functions, further define boundaries that provide for allosteric cGMP binding, and identify regions that contribute to dimerization...
  49. ncbi request reprint Stimulation of serotonin transport by the cyclic GMP phosphodiesterase-5 inhibitor sildenafil
    Chong Bin Zhu
    Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Eur J Pharmacol 504:1-6. 2004
    ..These findings implicate cGMP-targeted PDEs in limiting the regulation of antidepressant-sensitive 5-HT transport...
  50. ncbi request reprint Vardenafil: structural basis for higher potency over sildenafil in inhibiting cGMP-specific phosphodiesterase-5 (PDE5)
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, TN 37232 0615, USA
    Neurochem Int 45:859-63. 2004
    ....
  51. ncbi request reprint Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation
    Mitsi A Blount
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Mol Pharmacol 66:144-52. 2004
    ..Without inhibitor present, cGMP accumulation would stimulate cGMP degradation, but with inhibitor present, this negative feedback process would be blocked...
  52. ncbi request reprint Allosteric sites of phosphodiesterase-5 sequester cyclic GMP
    Jun Kotera
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Front Biosci 9:378-86. 2004
    ..This could provide for negative feedback control of cGMP-signaling...
  53. ncbi request reprint Molecular biology and pharmacology of PDE-5-inhibitor therapy for erectile dysfunction
    Jackie D Corbin
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0615, USA
    J Androl 24:S38-41. 2003
  54. ncbi request reprint Cyclic nucleotide specific phosphodiesterases of the kinetoplastida: a unified nomenclature
    Stefan Kunz
    Institute of Cell Biology, University of Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland
    Mol Biochem Parasitol 145:133-5. 2006