Focco van den Akker

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. ncbi Crystal structures of KPC-2 β-lactamase in complex with 3-nitrophenyl boronic acid and the penam sulfone PSR-3-226
    Wei Ke
    Departments of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA
    Antimicrob Agents Chemother 56:2713-8. 2012
  2. ncbi Crystal structure of the signaling helix coiled-coil domain of the beta1 subunit of the soluble guanylyl cyclase
    Xiaolei Ma
    Department of Biochemistry RT500, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA
    BMC Struct Biol 10:2. 2010
  3. ncbi Effect of the inhibitor-resistant M69V substitution on the structures and populations of trans-enamine beta-lactamase intermediates
    Monica A Totir
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 45:11895-904. 2006
  4. ncbi High resolution crystal structures of the trans-enamine intermediates formed by sulbactam and clavulanic acid and E166A SHV-1 {beta}-lactamase
    Pius S Padayatti
    Department of Biochemistry, Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 280:34900-7. 2005
  5. ncbi Rational design of a beta-lactamase inhibitor achieved via stabilization of the trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 complex with a penam sulfone
    Pius S Padayatti
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Am Chem Soc 128:13235-42. 2006
  6. ncbi Raman crystallographic studies of the intermediates formed by Ser130Gly SHV, a beta-lactamase that confers resistance to clinical inhibitors
    Marion S Helfand
    Research Service and Infectious Diseases Section, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA
    Biochemistry 46:8689-99. 2007
  7. ncbi Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase
    Faye Martin
    Department of Biochemistry RT500, Case Western Reserve University, Cleveland, Ohio 44120, USA
    J Biol Chem 285:22651-7. 2010
  8. ncbi Strategic design of an effective beta-lactamase inhibitor: LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone
    Priyaranjan Pattanaik
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 284:945-53. 2009
  9. ncbi Crystal structure of KPC-2: insights into carbapenemase activity in class A beta-lactamases
    Wei Ke
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106 4935, USA
    Biochemistry 46:5732-40. 2007
  10. ncbi PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure
    Xiaolei Ma
    Department of Biochemistry RT500, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 283:1167-78. 2008

Research Grants

  1. Atrial natriuretic peptide receptor crystallization
    Focco van den Akker; Fiscal Year: 2004
  2. Mechanism of activation of natriuretic peptide receptors
    Focco van den Akker; Fiscal Year: 2007
  3. Mechanistic studies and inhibition strategies for antibiotic resistance
    Focco van den Akker; Fiscal Year: 2007
  4. Mechanistic studies and inhibition strategies for antibiotic resistance
    Focco van den Akker; Fiscal Year: 2010

Collaborators

Detail Information

Publications17

  1. ncbi Crystal structures of KPC-2 β-lactamase in complex with 3-nitrophenyl boronic acid and the penam sulfone PSR-3-226
    Wei Ke
    Departments of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA
    Antimicrob Agents Chemother 56:2713-8. 2012
    ..3-NPBA and PSR-3-226 are the first β-lactamase inhibitors to be trapped as an acyl-enzyme complex with KPC-2. The structural and inhibitory insights gained here could aid in the design of potent KPC-2 inhibitors...
  2. ncbi Crystal structure of the signaling helix coiled-coil domain of the beta1 subunit of the soluble guanylyl cyclase
    Xiaolei Ma
    Department of Biochemistry RT500, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA
    BMC Struct Biol 10:2. 2010
    ..Homodimers of sGC have also been observed but are not functionally active yet are likely transient awaiting their intended heterodimeric partner...
  3. ncbi Effect of the inhibitor-resistant M69V substitution on the structures and populations of trans-enamine beta-lactamase intermediates
    Monica A Totir
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 45:11895-904. 2006
    ....
  4. ncbi High resolution crystal structures of the trans-enamine intermediates formed by sulbactam and clavulanic acid and E166A SHV-1 {beta}-lactamase
    Pius S Padayatti
    Department of Biochemistry, Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 280:34900-7. 2005
    ..These observations led us to conclude that the conformational stability of the trans-enamine form is critical for their transient inhibitory efficacy...
  5. ncbi Rational design of a beta-lactamase inhibitor achieved via stabilization of the trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 complex with a penam sulfone
    Pius S Padayatti
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Am Chem Soc 128:13235-42. 2006
    ..Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A beta-lactamase inhibitors...
  6. ncbi Raman crystallographic studies of the intermediates formed by Ser130Gly SHV, a beta-lactamase that confers resistance to clinical inhibitors
    Marion S Helfand
    Research Service and Infectious Diseases Section, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA
    Biochemistry 46:8689-99. 2007
    ..This finding has important implications in the design of beta-lactamase inhibitors for drug resistant variants like S130G SHV...
  7. ncbi Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase
    Faye Martin
    Department of Biochemistry RT500, Case Western Reserve University, Cleveland, Ohio 44120, USA
    J Biol Chem 285:22651-7. 2010
    ..The structure provides insights into how BAY 58-2667 binds and activates sGC to rescue heme-NO dysfunction in cardiovascular diseases...
  8. ncbi Strategic design of an effective beta-lactamase inhibitor: LN-1-255, a 6-alkylidene-2'-substituted penicillin sulfone
    Priyaranjan Pattanaik
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 284:945-53. 2009
    ..The 2'-substituted penicillin sulfone, LN-1-255, is proving to be an important lead compound for novel beta-lactamase inhibitor design...
  9. ncbi Crystal structure of KPC-2: insights into carbapenemase activity in class A beta-lactamases
    Wei Ke
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106 4935, USA
    Biochemistry 46:5732-40. 2007
    ..The structure of KPC-2 provides key insights into the carbapenemase activity of emerging class A beta-lactamases...
  10. ncbi PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure
    Xiaolei Ma
    Department of Biochemistry RT500, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 283:1167-78. 2008
    ..Our structural and mutational results provide new insights into sGC and STHK dimerization and overall architecture...
  11. ncbi Novel insights into the mode of inhibition of class A SHV-1 beta-lactamases revealed by boronic acid transition state inhibitors
    Wei Ke
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106 4935, USA
    Antimicrob Agents Chemother 55:174-83. 2011
    ..Both variants yielded improved affinity against SHV-1, possibly as a consequence of releasing the strain of its interaction with the unusual Y105 conformation...
  12. ncbi NO and CO differentially activate soluble guanylyl cyclase via a heme pivot-bend mechanism
    Xiaolei Ma
    Department of Biochemistry RT500, Case Western Reserve University, Cleveland, OH 44106, USA
    EMBO J 26:578-88. 2007
    ..This transition can be modulated by mutations at sGC residues 74 and 145 and corresponding residues in the cyanobacterial H-NOX homolog...
  13. ncbi Ligand-dependent disorder of the Omega loop observed in extended-spectrum SHV-type beta-lactamase
    Jared M Sampson
    Department of Biochemistry, Case Western University School of Medicine, Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA
    Antimicrob Agents Chemother 55:2303-9. 2011
    ....
  14. ncbi Structural insights into the regulation and the activation mechanism of mammalian guanylyl cyclases
    Pius S Padayatti
    Department of Biochemistry/RT500, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    Pharmacol Ther 104:83-99. 2004
    ..These efforts contribute to an enhanced understanding of the GC and will likely lead to an increased success in structure-based therapeutic intervention...
  15. ncbi Expression, purification, and characterization of the intra-cellular domain of the ANP receptor
    Priyaranjan Pattanaik
    Department of Biochemistry RT500, Case Western Reserve University, 10900 Euclid Av, Cleveland, OH 44106, USA
    Biochimie 91:888-93. 2009
    ..These receptor insights could aid in the development of novel therapeutics as the GCA receptor is a key drug target for cardiovascular diseases...
  16. ncbi Expression and crystallization of several forms of the Propionibacterium shermanii transcarboxylase 5S subunit
    Pamela R Hall
    Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Acta Crystallogr D Biol Crystallogr 60:521-3. 2004
    ..All 5S crystals diffract to approximately 2.0 A resolution with synchrotron radiation. Efforts are under way to solve the structure of SeMet-5S-His(6) using MAD...
  17. ncbi Tazobactam forms a stoichiometric trans-enamine intermediate in the E166A variant of SHV-1 beta-lactamase: 1.63 A crystal structure
    Pius S Padayatti
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106 4935, USA
    Biochemistry 43:843-8. 2004
    ..Understanding the structural details of differing inhibitor effectiveness can aid the design of improved mechanism-based beta-lactamase inhibitors...

Research Grants9

  1. Atrial natriuretic peptide receptor crystallization
    Focco van den Akker; Fiscal Year: 2004
    ..Our long term structural studies on the molecular mechanism of ANP receptor signaling could enhance the development of renal and cardiovascular drugs. ..
  2. Mechanism of activation of natriuretic peptide receptors
    Focco van den Akker; Fiscal Year: 2007
    ..These proposed studies on natriuretic peptide receptors will increase our understanding of mechanisms of activation and function, and could enhance the development of new renal, cardiovascular, or skeletal growth stimulatory drugs. ..
  3. Mechanistic studies and inhibition strategies for antibiotic resistance
    Focco van den Akker; Fiscal Year: 2007
    ..pneumoniae in New York. These resistance insights will lead to new therapeutic approaches and our goal is to study and develop new broad-spectrum beta-lactamase inhibitors. ..
  4. Mechanistic studies and inhibition strategies for antibiotic resistance
    Focco van den Akker; Fiscal Year: 2010
    ..pneumoniae in New York. These resistance insights will lead to new therapeutic approaches and our goal is to study and develop new broad-spectrum beta-lactamase inhibitors. ..