PETER GETTINS

Summary

Affiliation: University of Illinois at Chicago
Country: USA

Publications

  1. pmc A proximal pair of positive charges provides the dominant ligand-binding contribution to complement-like domains from the LRP (low-density lipoprotein receptor-related protein)
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA
    Biochem J 443:65-73. 2012
  2. pmc Receptor-associated protein (RAP) has two high-affinity binding sites for the low-density lipoprotein receptor-related protein (LRP): consequences for the chaperone functions of RAP
    Jan K Jensen
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland, M C 669, Chicago, IL 60607, USA
    Biochem J 421:273-82. 2009
  3. ncbi request reprint Use of NMR to study serpin function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, M C 669, University of Illinois at Chicago, 900 South Ashland, Chicago, IL 60607, USA
    Methods 32:120-9. 2004
  4. ncbi request reprint The F-helix of serpins plays an essential, active role in the proteinase inhibition mechanism
    Peter G W Gettins
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, 60612 4316, Chicago, IL, USA
    FEBS Lett 523:2-6. 2002
  5. pmc Activation of antithrombin as a factor IXa and Xa inhibitor involves mitigation of repression rather than positive enhancement
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, and Center for Structural Biology, University of Illinois at Chicago, IL 60612 4316, USA
    FEBS Lett 583:3397-400. 2009
  6. ncbi request reprint Serpin structure, mechanism, and function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M C 536, 1819 53 West Polk Street, Chicago, Illinois 60612, USA
    Chem Rev 102:4751-804. 2002
  7. pmc Exosite determinants of serpin specificity
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Biol Chem 284:20441-5. 2009
  8. ncbi request reprint Use of fluorescence resonance energy transfer to study serpin-proteinase interactions
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, M C 669, University of Illinois at Chicago, Chicago, IL 60607, USA
    Methods 32:110-9. 2004
  9. pmc Specificity and reactive loop length requirements for crmA inhibition of serine proteases
    Lisa D Tesch
    Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA
    Protein Sci 14:533-42. 2005
  10. ncbi request reprint Active site distortion is sufficient for proteinase inhibition by serpins: structure of the covalent complex of alpha1-proteinase inhibitor with porcine pancreatic elastase
    Alexey Dementiev
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 281:3452-7. 2006

Research Grants

  1. LRP structure and function
    Peter G W Gettins; Fiscal Year: 2011
  2. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2007
  3. FUNCTION AND DYSFUNCTION IN HUMAN ANTITHROMBINS
    PETER GETTINS; Fiscal Year: 2007
  4. Protein interactions by analytical ultracentrifugation
    PETER GETTINS; Fiscal Year: 2007
  5. 900MHz NMR for Structural Biology in Chicago
    PETER GETTINS; Fiscal Year: 2007
  6. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2009
  7. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2009
  8. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2007
  9. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2006
  10. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2006

Collaborators

Detail Information

Publications34

  1. pmc A proximal pair of positive charges provides the dominant ligand-binding contribution to complement-like domains from the LRP (low-density lipoprotein receptor-related protein)
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA
    Biochem J 443:65-73. 2012
    ..Together these findings establish the rules for determining the binding specificity of protein ligands to LRP and to other LDLR (low-density lipoprotein receptor) family members...
  2. pmc Receptor-associated protein (RAP) has two high-affinity binding sites for the low-density lipoprotein receptor-related protein (LRP): consequences for the chaperone functions of RAP
    Jan K Jensen
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland, M C 669, Chicago, IL 60607, USA
    Biochem J 421:273-82. 2009
    ..These findings suggest a new model for RAP to function as a folding chaperone and also for the involvement of YWTD domains in RAP release from LRP in the Golgi...
  3. ncbi request reprint Use of NMR to study serpin function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, M C 669, University of Illinois at Chicago, 900 South Ashland, Chicago, IL 60607, USA
    Methods 32:120-9. 2004
    ....
  4. ncbi request reprint The F-helix of serpins plays an essential, active role in the proteinase inhibition mechanism
    Peter G W Gettins
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, 60612 4316, Chicago, IL, USA
    FEBS Lett 523:2-6. 2002
    ..The F-helix is therefore not a passive impediment to proteinase translocation, but a critical, active element in permitting the serpin inhibition mechanism to operate successfully...
  5. pmc Activation of antithrombin as a factor IXa and Xa inhibitor involves mitigation of repression rather than positive enhancement
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, and Center for Structural Biology, University of Illinois at Chicago, IL 60612 4316, USA
    FEBS Lett 583:3397-400. 2009
    ....
  6. ncbi request reprint Serpin structure, mechanism, and function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M C 536, 1819 53 West Polk Street, Chicago, Illinois 60612, USA
    Chem Rev 102:4751-804. 2002
  7. pmc Exosite determinants of serpin specificity
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Biol Chem 284:20441-5. 2009
    ..A frequent theme is down-regulation of inhibitory activity unless the exosite(s) are engaged. In addition, the use of exosites by maspin and plasminogen activator inhibitor-1 to indirectly affect proteolytic processes is considered...
  8. ncbi request reprint Use of fluorescence resonance energy transfer to study serpin-proteinase interactions
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, M C 669, University of Illinois at Chicago, Chicago, IL 60607, USA
    Methods 32:110-9. 2004
    ..However, care must be taken to ensure that measurements made represent sufficient overdetermination that the answer obtained is unambiguous...
  9. pmc Specificity and reactive loop length requirements for crmA inhibition of serine proteases
    Lisa D Tesch
    Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA
    Protein Sci 14:533-42. 2005
    ..These results indicate that crmA inhibits serine proteases by the established serpin conformational trapping mechanism, but is unusual in inhibiting through either of two adjacent reactive sites...
  10. ncbi request reprint Active site distortion is sufficient for proteinase inhibition by serpins: structure of the covalent complex of alpha1-proteinase inhibitor with porcine pancreatic elastase
    Alexey Dementiev
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 281:3452-7. 2006
    ..The present structure shows that active site distortion alone is sufficient for inhibition and suggests that enhanced proteolysis is not necessarily exploited in vivo...
  11. ncbi request reprint Dissection of RAP-LRP interactions: binding of RAP and RAP fragments to complement-like repeats 7 and 8 from ligand binding cluster II of LRP
    Ana Lazic
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
    Arch Biochem Biophys 450:167-75. 2006
    ....
  12. pmc Basis for the specificity and activation of the serpin protein Z-dependent proteinase inhibitor (ZPI) as an inhibitor of membrane-associated factor Xa
    Xin Huang
    Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 285:20399-409. 2010
    ....
  13. ncbi request reprint alpha1-Proteinase inhibitor forms initial non-covalent and final covalent complexes with elastase analogously to other serpin-proteinase pairs, suggesting a common mechanism of inhibition
    József Dobó
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 279:9264-9. 2004
    ..It is likely that the material used by Mellet and Bieth contained such active elastase, resulting in mistaken attribution of the behavior of covalent complex to that of the non-covalent complex...
  14. ncbi request reprint Serine and cysteine proteases are translocated to similar extents upon formation of covalent complexes with serpins. Fluorescence perturbation and fluorescence resonance energy transfer mapping of the protease binding site in CrmA complexes with granzyme
    Richard Swanson
    Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 282:2305-13. 2007
    ....
  15. pmc Characterization of the conformational alterations, reduced anticoagulant activity, and enhanced antiangiogenic activity of prelatent antithrombin
    Benjamin Richard
    Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA
    J Biol Chem 283:14417-29. 2008
    ..Together, these results demonstrate that limited conformational alterations of antithrombin that modestly reduce anticoagulant activity are sufficient to generate antiangiogenic activity...
  16. ncbi request reprint The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity
    Alexey Dementiev
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, 900 S Ashland, Chicago, Illinois 60607, USA
    Nat Struct Mol Biol 11:863-7. 2004
    ..The protein-protein and protein-oligosaccharide interactions together explain the basis for heparin activation of antithrombin as a thrombin inhibitor...
  17. ncbi request reprint Crystal structure of human maspin, a serpin with antitumor properties: reactive center loop of maspin is exposed but constrained
    Maher Al-Ayyoubi
    Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, 835 S Wolcott Avenue, Chicago, IL 60612 7334
    J Biol Chem 279:55540-4. 2004
    ..These structural results will contribute to our understanding of the mechanism by which Maspin suppresses tumors...
  18. pmc Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. A paradigm for understanding proteinase regulation by serpin family protein proteinase inhibitors
    Steven T Olson
    Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA
    Biochimie 92:1587-96. 2010
    ....
  19. ncbi request reprint Maspin binds to urokinase-type and tissue-type plasminogen activator through exosite-exosite interactions
    Maher Al-Ayyoubi
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 282:19502-9. 2007
    ....
  20. ncbi request reprint Lack of involvement of strand s1'A of the viral serpin CrmA in anti-apoptotic or caspase-inhibitory functions
    Miljan Simonovic
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, USA
    Arch Biochem Biophys 440:1-9. 2005
    ..Thus, although the 51-56 region of CrmA is unique, and is exposed and highly susceptible to proteolysis, any in vivo role must involve a function other than proteinase inhibition or cell sparing...
  21. pmc Characterization of the LDL-A module mutants of Tva, the subgroup A Rous sarcoma virus receptor, and the implications in protein folding
    Qing Yin Wang
    Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    Protein Sci 11:2596-605. 2002
    ..Furthermore, these results suggest that the familial hypercholesterolemia (FH) French Canadian-4 mutation is likely caused by protein misfolding of low-density lipoprotein receptor, thus explaining the defect for this class of FH...
  22. pmc Structural similarity of the covalent complexes formed between the serpin plasminogen activator inhibitor-1 and the arginine-specific proteinases trypsin, LMW u-PA, HMW u-PA, and t-PA: use of site-specific fluorescent probes of local environment
    Marija Backovic
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, 1853 West Polk Street, Chicago, IL 60612, USA
    Protein Sci 11:1182-91. 2002
    ....
  23. pmc Specificity of binding of the low density lipoprotein receptor-related protein to different conformational states of the clade E serpins plasminogen activator inhibitor-1 and proteinase nexin-1
    Jan K Jensen
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 284:17989-97. 2009
    ..This may be sufficient to give preferential binding of such complexes in vivo at the relevant physiological concentrations...
  24. ncbi request reprint Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases
    Alexey Dementiev
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 278:37881-7. 2003
    ..This suggests a general, limited, canonical-like interaction between serpins and proteinases in their Michaelis complexes...
  25. ncbi request reprint Pigment epithelium-derived factor (PEDF), a serpin with potent anti-angiogenic and neurite outgrowth-promoting properties
    Peter G W Gettins
    Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, Chicago, IL 60612, USA
    Biol Chem 383:1677-82. 2002
    ..The determination of a high resolution X-ray crystal structure of native PEDF provides insight into regions of the protein that may be involved in one or more of these functions...
  26. pmc Kinetic analysis of binding interaction between the subgroup A Rous sarcoma virus glycoprotein SU and its cognate receptor Tva: calcium is not required for ligand binding
    Xuemei Yu
    Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Virol 77:7517-26. 2003
    ..Thus, these results may have broad implications for the mechanism of protein folding and ligand recognition of the LDL receptor and other members of the LDL receptor superfamily...
  27. ncbi request reprint Insight into residues critical for antithrombin function from analysis of an expanded database of sequences that includes frog, turtle, and ostrich antithrombins
    Marija Backovic
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612 4316, USA
    J Proteome Res 1:367-73. 2002
    ..Importantly, an understanding of, as yet, poorly understood antithrombin-protein interactions will be greatly aided by this expanded database and comparative analysis...
  28. pmc High-resolution structure of the stable plasminogen activator inhibitor type-1 variant 14-1B in its proteinase-cleaved form: a new tool for detailed interaction studies and modeling
    Jan K Jensen
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Protein Sci 17:1844-9. 2008
    ..This high-resolution structure should be of great use for drug target development and for modeling protein-protein interactions such as those of PAI-1 with vitronectin...
  29. ncbi request reprint Structural organization of the receptor associated protein
    Ana Lazic
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607 7170, USA
    Biochemistry 42:14913-20. 2003
    ..Whereas domains 1D and 2D do not interact with one another, 3D interacts with 2D, both in a 2D-3D construct and in intact RAP. Sedimentation measurements also indicated that intact RAP, although monomeric, is significantly elongated...
  30. ncbi request reprint Cytokine response modifier a inhibition of initiator caspases results in covalent complex formation and dissociation of the caspase tetramer
    József Dobó
    Department of Biochemistry and Molecular Genetics, University of Illinois, 900 S Ashland, Chicago, IL 60607, USA
    J Biol Chem 281:38781-90. 2006
    ....
  31. ncbi request reprint Three complement-like repeats compose the complete alpha2-macroglobulin binding site in the second ligand binding cluster of the low density lipoprotein receptor-related protein
    Klavs Dolmer
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Biol Chem 281:34189-96. 2006
    ....
  32. pmc Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3
    Ninh Doan
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, U S A
    Biochem J 407:23-30. 2007
    ....
  33. ncbi request reprint Importance of lysine 125 for heparin binding and activation of antithrombin
    Sophia Schedin-Weiss
    Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala
    Biochemistry 41:4779-88. 2002
    ..These effects are exerted by interactions of Lys125 with the nonreducing end of the heparin pentasaccharide...
  34. ncbi request reprint Helix D elongation and allosteric activation of antithrombin
    Klara J Belzar
    Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Rd, Cambridge CB2 2XY, United Kingdom
    J Biol Chem 277:8551-8. 2002
    ..We conclude that helix D elongation is critical for the full conversion of antithrombin to its high affinity, activated state, and we propose a mechanism to explain how helix D elongation is coupled to allosteric activation...

Research Grants23

  1. LRP structure and function
    Peter G W Gettins; Fiscal Year: 2011
    ..Our goal is to advance understanding of the mechanisms whereby LRP1 participates in these systems. Such knowledge could be of great use in designing specific drugs to target different functions of LRP1. ..
  2. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2007
    ..Dudley Strickland. ..
  3. FUNCTION AND DYSFUNCTION IN HUMAN ANTITHROMBINS
    PETER GETTINS; Fiscal Year: 2007
    ..For antithrombins that have been activated by mutation, x-ray crystallography, through collaboration with Dr. Robin Carrell, will be used...
  4. Protein interactions by analytical ultracentrifugation
    PETER GETTINS; Fiscal Year: 2007
    ..The knowledge gained will be invaluable for design of therapeutics against such infections or in amelioration of diseases associated with aberrant functioning of processes such as blood coagulation. ..
  5. 900MHz NMR for Structural Biology in Chicago
    PETER GETTINS; Fiscal Year: 2007
    ..As part of the facility, a resource will be established for development of procedures for intein-based segmental isotopic labeling of proteins, as well as for production of segmentally labeled DNA and RNA species. ..
  6. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2009
    ..abstract_text> ..
  7. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2009
    ..Dudley Strickland. ..
  8. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2007
    ..Tryptophan variants of intact alpha2M will enable fluorescence to be used to map domain reorganizations upon activation of the alpha2M. ..
  9. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2006
    ..Tryptophan variants of intact alpha2M will enable fluorescence to be used to map domain reorganizations upon activation of the alpha2M. ..
  10. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2006
    ..Dudley Strickland. ..
  11. STRUCTURE AND FUNCTION OF ALPHA-2 MACROGLOBULIN
    PETER GETTINS; Fiscal Year: 1999
    ....
  12. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2000
    ..The presence of such variants in plasma from Alzheimer's patients will be determined. ..
  13. ACQUISITION OF CRYOPROBE FOR 600 MHZ NMR SPECTROMETER
    PETER GETTINS; Fiscal Year: 2001
    ..600MHz spectrometer, will derive immediate benefit from this probe, those of Michael Caffrey, Xiubei Liao and Peter Gettins in the College of Medicine and Michael Johnson in the College of Pharmacy, in collaboration with Leslie Fung ..
  14. ULTRASENSITIVE CALORIMETRY SYSTEM FOR BIOMOLECULES
    PETER GETTINS; Fiscal Year: 2001
    ..abstract_text> ..
  15. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2001
    ..The presence of such variants in plasma from Alzheimer's patients will be determined. ..
  16. 3rd Intl Symp on Serpin Biology, Structure and Function
    PETER GETTINS; Fiscal Year: 2002
    ..v) To provide an opportunity for promising junior scientists and minorities to play a major role in the meeting. ..
  17. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2002
    ..The presence of such variants in plasma from Alzheimer's patients will be determined. ..
  18. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    PETER GETTINS; Fiscal Year: 2003
    ..The presence of such variants in plasma from Alzheimer's patients will be determined. ..
  19. STRUCTURE/FUNCTION OF ALPHA2M AND ITS RECEPTOR LRP
    Peter G W Gettins; Fiscal Year: 2010
    ..abstract_text> ..