Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes

Li, Mi; Srp, Jaroslav; Gustchina, Alla; Dauter, Zbigniew; Mares, Michael; Wlodawer, Alexander

doi:10.1107/S2059798318016492

Title: Crystal structures of the complex of a kallikrein inhibitor from Bauhinia bauhinioides with trypsin and modeling of kallikrein complexes

Journal Article · Tue Jan 01 00:00:00 EST 2019 · Acta Crystallographica. Section D. Structural Biology

DOI:https://doi.org/10.1107/S2059798318016492· OSTI ID:1506508

Li, Mi;

; Gustchina, Alla; Dauter, Zbigniew; Mares, Michael; Wlodawer, Alexander

Structures of a recombinant Kunitz-type serine protease inhibitor from Bauhinia bauhinioides (BbKI) complexed with bovine trypsin were determined in two crystal forms. The crystal structure with the L55R mutant of BbKI was determined in space group P6₄at 1.94 Å resolution and that with native BbKI in the monoclinic space group P2₁at 3.95 Å resolution. The asymmetric unit of the latter crystals contained 44 independent complexes, thus representing one of the largest numbers of independent objects deposited in the Protein Data Bank. Additionally, the structure of the complex with native BbKI was determined at 2.0 Å resolution from P6₄crystals isomorphous to those of the mutant. Since BbKI has previously been found to be a potent inhibitor of the trypsin-like plasma kallikrein, it was also tested against several tissue kallikreins. It was found that BbKI is a potent inhibitor of human tissue kallikrein 4 (KLK4) and the chymotrypsin-like human tissue kallikrein 7 (KLK7). Structures of BbKI complexed with the catalytic domain of human plasma kallikrein were modeled, as well as those with KLK4 and KLK7, and the structures were analyzed in order to identify the interactions that are responsible for inhibitory potency.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1506508

Journal Information:: Acta Crystallographica. Section D. Structural Biology, Vol. 75, Issue 1; ISSN 2059-7983

Publisher:: IUCr

Country of Publication:: United States

Language:: ENGLISH

References (48)

Differences in substrate and inhibitor sequence specificity of human, mouse and rat tissue kallikreins FogaÇA, Sandro E.; Melo, Robson L.; Pimenta, Daniel C. Biochemical Journal, Vol. 380, Issue 3 https://doi.org/10.1042/bj20031047	journal	June 2004
Crystal Structures of a Plant Trypsin Inhibitor from Enterolobium contortisiliquum (EcTI) and of Its Complex with Bovine Trypsin Zhou, Dongwen; Lobo, Yara A.; Batista, Isabel F. C. PLoS ONE, Vol. 8, Issue 4 https://doi.org/10.1371/journal.pone.0062252	journal	April 2013
Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics Riley, Blake T.; Ilyichova, Olga; Costa, Mauricio G. S. Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep35385	journal	October 2016
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
The crystal structures of the complexes between bovine β-trypsin and ten P1 variants of BPTI Helland, Ronny; Otlewski, Jacek; Sundheim, Ottar Journal of Molecular Biology, Vol. 287, Issue 5 https://doi.org/10.1006/jmbi.1999.2654	journal	April 1999
Structural basis for dual inhibitory role of tamarind Kunitz inhibitor (TKI) against factor Xa and trypsin Patil, Dipak N.; Chaudhary, Anshul; Sharma, Ashwani K. FEBS Journal, Vol. 279, Issue 24 https://doi.org/10.1111/febs.12042	journal	November 2012
Crystal structure analysis of icosahedral lumazine synthase from Salmonella typhimurium , an antibacterial drug target Kumar, Pankaj; Singh, Mirage; Karthikeyan, Subramanian Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 2 https://doi.org/10.1107/S0907444910053370	journal	January 2011
Scalable molecular dynamics with NAMD Phillips, James C.; Braun, Rosemary; Wang, Wei Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802 https://doi.org/10.1002/jcc.20289	journal	January 2005
Mastering the Canonical Loop of Serine Protease Inhibitors: Enhancing Potency by Optimising the Internal Hydrogen Bond Network Swedberg, Joakim E.; de Veer, Simon J.; Sit, Kei C. PLoS ONE, Vol. 6, Issue 4 https://doi.org/10.1371/journal.pone.0019302	journal	April 2011
Targeting kallikrein-related peptidases in prostate cancer Mavridis, Konstantinos; Avgeris, Margaritis; Scorilas, Andreas Expert Opinion on Therapeutic Targets, Vol. 18, Issue 4 https://doi.org/10.1517/14728222.2014.880693	journal	February 2014
Blocking the Proliferation of Human Tumor Cell Lines by Peptidase Inhibitors from Bauhinia Seeds Nakahata, Adriana; Mayer, Barbara; Neth, Peter Planta Medica, Vol. 79, Issue 03/04 https://doi.org/10.1055/s-0032-1328156	journal	January 2013
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Isolation of a Crystalline Protein Compound of Trypsin and of Soybean Trypsin-Inhibitor Kunitz, M. The Journal of General Physiology, Vol. 30, Issue 4 https://doi.org/10.1085/jgp.30.4.311	journal	March 1947
Targeting the kallikrein-related peptidases for drug development Sotiropoulou, Georgia; Pampalakis, Georgios Trends in Pharmacological Sciences, Vol. 33, Issue 12 https://doi.org/10.1016/j.tips.2012.09.005	journal	December 2012
Structure of BbKI, a disulfide-free plasma kallikrein inhibitor Zhou, Dongwen; Hansen, Daiane; Shabalin, Ivan G. Acta Crystallographica Section F Structural Biology Communications, Vol. 71, Issue 8 https://doi.org/10.1107/S2053230X15011127	journal	July 2015
Primary structure of a Kunitz-type trypsin inhibitor from Enterolobium contortisiliquum seeds Batista, Isabel F. C.; Oliva, Maria Luiza V.; Araujo, Mariana S. Phytochemistry, Vol. 41, Issue 4 https://doi.org/10.1016/0031-9422(95)00710-5	journal	March 1996
The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models Brito, Marlon V.; de Oliveira, Cleide; Salu, Bruno R. Thrombosis Research, Vol. 133, Issue 5 https://doi.org/10.1016/j.thromres.2014.02.027	journal	May 2014
REFMAC 5 for the refinement of macromolecular crystal structures Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911001314	journal	March 2011
Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors Li, Zhe; Partridge, James; Silva-Garcia, Abel ACS Medicinal Chemistry Letters, Vol. 8, Issue 2 https://doi.org/10.1021/acsmedchemlett.6b00384	journal	December 2016
Discovery and structure–activity relationship study of 1,3,6-trisubstituted 1,4-diazepane-7-ones as novel human kallikrein 7 inhibitors Murafuji, Hidenobu; Sakai, Hiroki; Goto, Megumi Bioorganic & Medicinal Chemistry Letters, Vol. 27, Issue 23 https://doi.org/10.1016/j.bmcl.2017.10.030	journal	December 2017
Biochemical characterization of Acacia schweinfurthii serine proteinase inhibitor Odei-Addo, Frank; Frost, Carminita; Smith, Nanette Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 29, Issue 5 https://doi.org/10.3109/14756366.2013.836642	journal	September 2013
Unleashing the therapeutic potential of human kallikrein-related serine proteases Prassas, Ioannis; Eissa, Azza; Poda, Gennadiy Nature Reviews Drug Discovery, Vol. 14, Issue 3 https://doi.org/10.1038/nrd4534	journal	February 2015
The expanding diversity of serine hydrolases Botos, Istvan; Wlodawer, Alexander Current Opinion in Structural Biology, Vol. 17, Issue 6 https://doi.org/10.1016/j.sbi.2007.08.003	journal	December 2007
Role of remote scaffolding residues in the inhibitory loop pre-organization, flexibility, rigidification and enzyme inhibition of serine protease inhibitors Majumder, Sudip; Khamrui, Susmita; Dasgupta, Jhimli Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1824, Issue 7 https://doi.org/10.1016/j.bbapap.2012.04.009	journal	July 2012
Structure and Mechanisms of a Protein-Based Organelle in Escherichia coli Tanaka, S.; Sawaya, M. R.; Yeates, T. O. Science, Vol. 327, Issue 5961 https://doi.org/10.1126/science.1179513	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Kallikrein-related peptidases targeted therapies in prostate cancer: perspectives and challenges Cereda, Vittore; Formica, Vincenzo; Menghi, Antonello Expert Opinion on Investigational Drugs, Vol. 24, Issue 7 https://doi.org/10.1517/13543784.2015.1035708	journal	April 2015
Identity of the tryptic and α-chymotrypic reactive sites on soybean trypsin inhibitor (Kunitz) Bidlingmeyer, Ursula De Vonis; Leary, T. Richard; Laskowski, Michael Biochemistry, Vol. 11, Issue 17 https://doi.org/10.1021/bi00767a028	journal	August 1972
Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines Hinkes, Stefan; Wuttke, André; Saupe, Sebastian M. Journal of Medicinal Chemistry, Vol. 59, Issue 13 https://doi.org/10.1021/acs.jmedchem.6b00606	journal	June 2016
Bauhinia bauhinioides Plasma Kallikrein Inhibitor Interaction with Synthetic Peptides and Fluorogenic Peptide Substrates Related to the Reactive Site Sequence Oliva, M. L.; Mendes, C.; Santomauro-Vaz, E. Current Medicinal Chemistry, Vol. 8, Issue 8 https://doi.org/10.2174/0929867013372779	journal	July 2001
Kunitz-type Bauhinia bauhinioides inhibitors devoid of disulfide bridges: isolation of the cDNAs, heterologous expression and structural studies Araújo, Ana Paula Ulian; Hansen, Daiane; Vieira, Debora F. Biological Chemistry, Vol. 386, Issue 6 https://doi.org/10.1515/BC.2005.066	journal	January 2005
Effect of a serine proteinase inhibitor fromLeucaena leucocephala on plasma kallikrein and plasmin Souza-Pinto, Jose C.; Oliva, Maria L. V.; Sampaio, Claudio A. M. Immunopharmacology, Vol. 33, Issue 1-3 https://doi.org/10.1016/0162-3109(96)00056-2	journal	June 1996
Characterization of a tissue kallikrein inhibitor isolated from Bauhinia bauhinioides seeds: inhibition of the hydrolysis of kininogen related substrates Oliva, Maria Luiza V.; R. Mendes, Catarina; Juliano, Maria A. Immunopharmacology, Vol. 45, Issue 1-3 https://doi.org/10.1016/S0162-3109(99)00075-2	journal	December 1999
All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins ^† MacKerell, A. D.; Bashford, D.; Bellott, M. The Journal of Physical Chemistry B, Vol. 102, Issue 18 https://doi.org/10.1021/jp973084f	journal	April 1998
Kunitz-type soybean trypsin inhibitor revisited: refined structure of its complex with porcine trypsin reveals an insight into the interaction between a homologous inhibitor from Erythrina caffra and tissue-type plasminogen activator 1 1Edited by R. Huber Song, Hyun Kyu; Suh, Se Won Journal of Molecular Biology, Vol. 275, Issue 2 https://doi.org/10.1006/jmbi.1997.1469	journal	January 1998
β-Trefoil inhibitors – from the work of Kunitz onward Renko, Miha; Sabotič, Jerica; Turk, Dušan Biological Chemistry, Vol. 393, Issue 10 https://doi.org/10.1515/hsz-2012-0159	journal	October 2012
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of alzheimer's amyloid β-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): Engineering of inhibitors with altered specificities Scheidig, Axel J.; Hynes, Thomas R.; Pelletier, Laura A. Protein Science, Vol. 6, Issue 9 https://doi.org/10.1002/pro.5560060902	journal	September 1997
Targeting proteases: successes, failures and future prospects Turk, Boris Nature Reviews Drug Discovery, Vol. 5, Issue 9 https://doi.org/10.1038/nrd2092	journal	September 2006
Free R value: a novel statistical quantity for assessing the accuracy of crystal structures Brünger, Axel T. Nature, Vol. 355, Issue 6359 https://doi.org/10.1038/355472a0	journal	January 1992
Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7 Debela, M.; Hess, P.; Magdolen, V. Proceedings of the National Academy of Sciences, Vol. 104, Issue 41 https://doi.org/10.1073/pnas.0707811104	journal	October 2007
Platelets Contain Tissue Factor Pathway Inhibitor-2 Derived from Megakaryocytes and Inhibits Fibrinolysis Vadivel, Kanagasabai; Ponnuraj, Sathya-Moorthy; Kumar, Yogesh Journal of Biological Chemistry, Vol. 289, Issue 45 https://doi.org/10.1074/jbc.M114.569665	journal	September 2014
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo The Journal of Physical Chemistry B, Vol. 114, Issue 23 https://doi.org/10.1021/jp101759q	journal	June 2010
A novel subclassification for Kunitz proteinase inhibitors from leguminous seeds Oliva, Maria Luiza V.; Silva, Mariana C. C.; Sallai, Roberto C. Biochimie, Vol. 92, Issue 11 https://doi.org/10.1016/j.biochi.2010.03.021	journal	November 2010
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Tying down the arm in Bacillus dUTPase: structure and mechanism García-Nafría, Javier; Timm, Jennifer; Harrison, Charlotte Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 8 https://doi.org/10.1107/S090744491300735X	journal	July 2013
Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models Horn, Martin; Zbodakova, Olga; Kasparek, Petr Biological Chemistry, Vol. 399, Issue 9 https://doi.org/10.1515/hsz-2018-0116	journal	September 2018
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007

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