Seungil Han

Summary

Affiliation: Pfizer Global Research and Development
Country: USA

Publications

  1. doi request reprint Distinctive attributes of β-lactam target proteins in Acinetobacter baumannii relevant to development of new antibiotics
    Seungil Han
    Pfizer Worldwide Research, Eastern Point Road, Groton, Connecticut 06340, USA
    J Am Chem Soc 133:20536-45. 2011
  2. pmc Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa
    Seungil Han
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Proc Natl Acad Sci U S A 107:22002-7. 2010
  3. pmc Structure of the adenylation domain of NAD(+)-dependent DNA ligase from Staphylococcus aureus
    Seungil Han
    Pfizer Inc, Groton, Connecticut 06340, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 65:1078-82. 2009
  4. pmc Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design
    Seungil Han
    Pfizer Global Research and Development, Groton, CT 06340, USA
    J Biol Chem 284:13193-201. 2009
  5. ncbi request reprint Crystal structure of nicotinic acid mononucleotide adenylyltransferase from Staphyloccocus aureus: structural basis for NaAD interaction in functional dimer
    Seungil Han
    Pfizer Inc Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    J Mol Biol 360:814-25. 2006
  6. pmc Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution
    Seungil Han
    Pfizer, Inc, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Protein Sci 16:2272-7. 2007
  7. doi request reprint Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation
    Daniel P Walker
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 18:6071-7. 2008
  8. doi request reprint Pyridone-conjugated monobactam antibiotics with gram-negative activity
    Matthew F Brown
    Worldwide Medicinal Chemistry, Computational Chemistry, Antibacterials Research Unit, Pharmacokinetics, Dynamics and Metabolism, Structural Biology, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States
    J Med Chem 56:5541-52. 2013
  9. pmc Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system
    Nicole L Caspers
    Structural Biology, Pfizer Inc, Eastern Point Road, Groton, CT 06340, USA
    Acta Crystallogr F Struct Biol Commun 72:840-845. 2016
  10. doi request reprint Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors
    Seungil Han
    Pfizer Worldwide Research, Eastern Point Road, Groton, CT 06340, U S A
    Biochem J 460:211-22. 2014

Detail Information

Publications23

  1. doi request reprint Distinctive attributes of β-lactam target proteins in Acinetobacter baumannii relevant to development of new antibiotics
    Seungil Han
    Pfizer Worldwide Research, Eastern Point Road, Groton, Connecticut 06340, USA
    J Am Chem Soc 133:20536-45. 2011
    ..The structural, biophysical, and computational data help rationalize differences in the functional performance of antibiotics against different protein targets and can be used to guide the design of future agents...
  2. pmc Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa
    Seungil Han
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Proc Natl Acad Sci U S A 107:22002-7. 2010
    ..Taken together, these structural, biochemical, and computational studies provide a molecular basis for recognition of P. aeruginosa PBP3 and open avenues for future design of inhibitors of this class of PBPs...
  3. pmc Structure of the adenylation domain of NAD(+)-dependent DNA ligase from Staphylococcus aureus
    Seungil Han
    Pfizer Inc, Groton, Connecticut 06340, USA
    Acta Crystallogr Sect F Struct Biol Cryst Commun 65:1078-82. 2009
    ..aureus DNA ligase structure provides a basis for a more integrated understanding of substrate recognition and catalysis and will be also be of help in the development of small-molecule inhibitors...
  4. pmc Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design
    Seungil Han
    Pfizer Global Research and Development, Groton, CT 06340, USA
    J Biol Chem 284:13193-201. 2009
    ..Our structural, biophysical, and pharmacological studies suggest that the unique features of the DFG motif, including Leu-504 hinge-loop variability, can be exploited for the development of selective protein kinase inhibitors...
  5. ncbi request reprint Crystal structure of nicotinic acid mononucleotide adenylyltransferase from Staphyloccocus aureus: structural basis for NaAD interaction in functional dimer
    Seungil Han
    Pfizer Inc Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    J Mol Biol 360:814-25. 2006
    ..Taken together, these structural results provide a molecular basis for understanding the coupled activity and recognition specificity for S. aureus NaMNAT and for rational design of selective inhibitors...
  6. pmc Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution
    Seungil Han
    Pfizer, Inc, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Protein Sci 16:2272-7. 2007
    ..Taken together, these structural features provide a molecular basis for understanding the coupled activity and recognition specificity for human ActRIIB kinase domain and for the rational design of selective inhibitors...
  7. doi request reprint Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation
    Daniel P Walker
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 18:6071-7. 2008
    ....
  8. doi request reprint Pyridone-conjugated monobactam antibiotics with gram-negative activity
    Matthew F Brown
    Worldwide Medicinal Chemistry, Computational Chemistry, Antibacterials Research Unit, Pharmacokinetics, Dynamics and Metabolism, Structural Biology, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States
    J Med Chem 56:5541-52. 2013
    ..In addition, evidence is provided for a number of analogues suggesting that the siderophore receptors PiuA and PirA play a role in drug uptake in P. aeruginosa strain PAO1. ..
  9. pmc Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system
    Nicole L Caspers
    Structural Biology, Pfizer Inc, Eastern Point Road, Groton, CT 06340, USA
    Acta Crystallogr F Struct Biol Commun 72:840-845. 2016
    ..This procedure could be useful for developing co-crystallization systems with an exchangeable ligand to enable structure-based drug design of other protein kinases...
  10. doi request reprint Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors
    Seungil Han
    Pfizer Worldwide Research, Eastern Point Road, Groton, CT 06340, U S A
    Biochem J 460:211-22. 2014
    ..An optimized lead showed exquisite kinome selectivity and is efficacious in human whole blood and proximal cell-based assays. ..
  11. doi request reprint Siderophore receptor-mediated uptake of lactivicin analogues in gram-negative bacteria
    Jeremy Starr
    Medicinal Chemistry, Computational Chemistry, Antibacterials Research Unit, and Structural Biology, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States
    J Med Chem 57:3845-55. 2014
    ..Finally, mechanistic studies demonstrating that sideromimic modification alters the drug uptake process are discussed. ..
  12. doi request reprint Expression and functional characterization of human lysosomal acid lipase gene (LIPA) mutation responsible for cholesteryl ester storage disease (CESD) phenotype
    Francis Rajamohan
    Pfizer Worldwide Research, Groton, CT 06340, USA Electronic address
    Protein Expr Purif 110:22-9. 2015
    ..The observed loss-of-function phenotype in CESD patients might arise from a combination of protein destabilization and the shift to a non-functional soluble aggregate. ..
  13. doi request reprint Redesigning and characterizing the substrate specificity and activity of Vibrio fluvialis aminotransferase for the synthesis of imagabalin
    Katarina S Midelfort
    Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Protein Eng Des Sel 26:25-33. 2013
    ..This work also provides insight into the critical residues for substrate specificity for the transamination of (R)-ethyl 5-methyl 3-oxooctanoate and structurally related β-ketoesters...
  14. doi request reprint Novel monobactams utilizing a siderophore uptake mechanism for the treatment of gram-negative infections
    Mark J Mitton-Fry
    Medicinal Chemistry, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 22:5989-94. 2012
    ..Novel siderophore-linked monobactams with in vitro and in vivo anti-microbial activity against MDR Gram-negative pathogens are described...
  15. doi request reprint Crystal structure of activin receptor type IIB kinase domain
    Seungil Han
    Pfizer Inc, Pfizer Global Research and Development, Groton, Connecticut, USA
    Vitam Horm 85:29-38. 2011
    ..The human ActRII kinase domain structure provides a basis for a more integrated understanding of substrate recognition and catalysis and will also be of help for developing chemical inhibitors...
  16. doi request reprint A systematic study of 50S ribosomal subunit purification enabling robust crystallization
    Thomas J McLellan
    Pfizer Inc, Department of Exploratory Medicinal Sciences, Pfizer Global Research and Development, Groton, CT 06340, USA
    Acta Crystallogr D Biol Crystallogr 65:1270-82. 2009
    ....
  17. doi request reprint Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity
    Daniel P Walker
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 19:3253-8. 2009
    ..In addition, compound (S)-14a shows good oral exposure in a rat pharmacokinetic model...
  18. ncbi request reprint Theoretical and experimental design of atypical kinase inhibitors: application to p38 MAP kinase
    Kim F McClure
    Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, USA
    J Med Chem 48:5728-37. 2005
    ..The computed descriptors for the hydrophobic and pi-pi interaction capacities were the most useful in ranking potency...
  19. doi request reprint Structural basis for AMPK activation: natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms
    Matthew F Calabrese
    Worldwide Research and Development, Pfizer Inc, Eastern Point Road, Groton, CT 06340, USA
    Structure 22:1161-72. 2014
    ..Our studies follow on the heels of the recent disclosure of the α2β1γ1 structure and provide insight into the distinct molecular mechanisms of AMPK regulation by AMP and A769662. ..
  20. ncbi request reprint WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing
    J Jefferson P Perry
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Nat Struct Mol Biol 13:414-22. 2006
    ..These results indicate WRN-exo is a human DnaQ family member and support DnaQ-like proofreading activities stimulated by Ku70/80, with implications for WRN functions in age-related pathologies and maintenance of genomic integrity...
  21. ncbi request reprint Tetrameric architecture of the circadian clock protein KaiB. A novel interface for intermolecular interactions and its impact on the circadian rhythm
    Kenichi Hitomi
    Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 280:19127-35. 2005
    ..KaiB antagonizes the action of KaiA on KaiC, and shares a sequence-homologous domain with the SasA kinase. Based on our structure, we discuss functional roles for KaiB in the circadian clock...
  22. ncbi request reprint Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in DNA replication and repair
    Brian R Chapados
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92122, USA
    Cell 116:39-50. 2004
    ....
  23. ncbi request reprint The ARTT motif and a unified structural understanding of substrate recognition in ADP-ribosylating bacterial toxins and eukaryotic ADP-ribosyltransferases
    Seungil Han
    Department of Molecular Biology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Int J Med Microbiol 291:523-9. 2002
    ....