Abstract
Enzymes are key biological macromolecules that support life by accelerating the conversion of target molecules to desired products in many biochemical reactions. Enzymes are characterized by high affinity, specificity and great catalytic efficiency. Owing to their unique characteristics, enzymes have attracted significant attention for use in therapeutic settings as a distinct class of drugs different from other types of medicines. Enzyme-based therapies are currently in use for the treatment of a wide range of diseases, including leukemia, metabolic disorders, inflammation and cardiovascular disease. However, several challenges, such as immunogenicity and stability, remain. X-ray crystallography has provided key structural insights into the understanding of the molecular basis of diseases and development of enzyme-based therapies. Here, the role of X-ray crystallography in the development of therapeutic enzymes is examined and several examples are provided.
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- ADI:
-
Arginine deiminase
- ASNase:
-
Asparaginase
- CHO:
-
Chinese hamster ovary
- DGJ:
-
1-deoxygalactonojirimycin
- DNJ:
-
1-deoxynojirimycin
- EcA:
-
E. coli ASNase
- ErA:
-
Erwinia chrysanthemi L-asparaginase
- ERT:
-
Enzyme replacement therapy
- GAA:
-
Acid alpha-glucosidase
- GAG:
-
Glycosaminoglycan
- GALC:
-
β-galactocerebrosidase
- GALNS:
-
N-acetylgalactosamine-6-sulfate sulfatase
- GCase:
-
Acid beta-glucosidase
- GD:
-
Gaucher disease
- GUSB:
-
β-glucuronidase
- IDS:
-
Iduronate-2-sulfatase
- IDUA:
-
α-L-iduronidase
- LK:
-
Lumbrokinase
- MPS:
-
Mucopolysaccharidosis
- NAC:
-
N-acetylcysteine
- NEP:
-
Neprilysin
- PAI-1:
-
Plasminogen activator inhibitor-1
- PAL:
-
Phenylalanine ammonia lyase
- PCT:
-
Pharmacological chaperone therapy
- PDB:
-
Protein data bank
- PEG:
-
Polyethylene glycol
- PKU:
-
Phenylketonuria
- SGSH:
-
N-sulfoglucosamine sulfohydrolase
- tPA:
-
Tissue plasminogen activator
- uPA:
-
Urokinase-type plasminogen activator
References
Aviezer D, Brill-Almon E, Shaaltiel Y, Hashmueli S, Bartfeld D, Mizrachi S, Liberman Y, Freeman A, Zimran A, Galun E (2009) A plant-derived recombinant human glucocerebrosidase enzyme – a preclinical and phase I investigation. PLoS One 4:e4792. https://doi.org/10.1371/journal.pone.0004792
Avramis VI (2011) Asparaginases: a successful class of drugs against leukemias and lymphomas. J Pediatr Hematol Oncol 33:573–579. https://doi.org/10.1097/MPH.0b013e31823313be
Bell SM, Wendt DJ, Zhang Y, Taylor TW, Long S, Tsuruda L, Zhao B, Laipis P, Fitzpatrick PA (2017) Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria. PLoS One 12:e0173269. https://doi.org/10.1371/journal.pone.0173269
Benjwal S, Verma S, Röhm K-H, Gursky O (2006) Monitoring protein aggregation during thermal unfolding in circular dichroism experiments. Protein Sci 15:635–639. https://doi.org/10.1110/ps.051917406
Bennett LL, Mohan D (2013) Gaucher disease and its treatment options. Ann Pharmacother 47:1182–1193. https://doi.org/10.1177/1060028013500469
Bie H, Yin J, He X, Kermode AR, Goddard-Borger ED, Withers SG, James MNG (2013) Insights into mucopolysaccharidosis I from the structure and action of α-L-iduronidase. Nat Chem Biol 9:739–745. https://doi.org/10.1038/nchembio.1357
Bijvoet AG, Van Hirtum H, Kroos MA, Van de Kamp EH, Schoneveld O, Visser P, Brakenhoff JP, Weggeman M, van Corven EJ, Van der Ploeg AT, Reuser AJ (1999) Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II. Hum Mol Genet 8:2145–2153
Bond CS, Clements PR, Ashby SJ, Collyer CA, Harrop SJ, Hopwood JJ, Guss JM (1997) Structure of a human lysosomal sulfatase. Structure 5:277–289
Brumshtein B, Wormald MR, Silman I, Futerman AH, Sussman JL (2006) Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease. Acta Crystallogr D Biol Crystallogr 62:1458–1465. https://doi.org/10.1107/S0907444906038303
Cai D, Zhu C, Chen S (2017) Microbial production of nattokinase: current progress, challenge and prospect. World J Microbiol Biotechnol 33:84. https://doi.org/10.1007/s11274-017-2253-2
Calabrese JC, Jordan DB, Boodhoo A, Sariaslani S, Vannelli T (2004) Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis. Biochemistry 43:11403–11416. https://doi.org/10.1021/bi049053
Chen K-C, Wu C-H, Chang C-Y, Lu W-C, Tseng Q, Prijovich ZM, Schechinger W, Liaw Y-C, Leu Y-L, Roffler SR (2008) Directed evolution of a lysosomal enzyme with enhanced activity at neutral pH by mammalian cell-surface display. Chem Biol 15:1277–1286. https://doi.org/10.1016/j.chembiol.2008.10.008
Das K, Butler GH, Kwiatkowski V, Clark AD, Yadav P, Arnold E (2004) Crystal structures of arginine deiminase with covalent reaction intermediates; implications for catalytic mechanism. Structure 12:657–667. https://doi.org/10.1016/j.str.2004.02.017
Deckert PM, Bornmann WG, Ritter G, Williams C, Franke J, Keilholz U, Thiel E, Old LJ, Bertino JR, Welt S (2004) Specific tumour localisation of a huA33 antibody – carboxypeptidase A conjugate and activation of methotrexate-phenylalanine. Int J Oncol 24:1289–1295
Demydchuk M, Hill CH, Zhou A, Bunkoczi G, Stein PE, Marchesan D, Deane JE, Read RJ (2017) Insights into Hunter syndrome from the structure of iduronate-2-sulfatase. Nat Commun 8:15786. https://doi.org/10.1038/ncomms15786
Desnick RJ, Schuchman EH (2012) Enzyme replacement therapy for lysosomal diseases: lessons from 20 years of experience and remaining challenges. Annu Rev Genomics Hum Genet 13:307–335. https://doi.org/10.1146/annurev-genom-090711-163739
Dhavala P, Papageorgiou AC (2009) Structure of helicobacter pylori L-asparaginase at 1.4 A resolution. Acta Crystallogr D Biol Crystallogr 65:1253–1261. https://doi.org/10.1107/S0907444909038244
Dodson G, Wlodawer A (1998) Catalytic triads and their relatives. Trends Biochem Sci 23:347–352
Dvir H, Harel M, McCarthy AA, Toker L, Silman I, Futerman AH, Sussman JL (2003) X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease. EMBO Rep 4:704–709. https://doi.org/10.1038/sj.embor.embor873
Galkin A, Lu X, Dunaway-Mariano D, Herzberg O (2005) Crystal structures representing the Michaelis complex and the thiouronium reaction intermediate of Pseudomonas aeruginosa arginine deiminase. J Biol Chem 280:34080–34087. https://doi.org/10.1074/jbc.M505471200
Gamez A, Sarkissian CN, Wang L, Kim W, Straub M, Patch MG, Chen L, Striepeke S, Fitzpatrick P, Lemontt JF, O’Neill C, Scriver CR, Stevens RC (2005) Development of pegylated forms of recombinant Rhodosporidium toruloides phenylalanine ammonia-lyase for the treatment of classical phenylketonuria. Mol Ther 11:986–989. https://doi.org/10.1016/j.ymthe.2005.02.013
Gong H, Zolzer F, von Recklinghausen G, Havers W, Schweigerer L (2000) Arginine deiminase inhibits proliferation of human leukemia cells more potently than asparaginase by inducing cell cycle arrest and apoptosis. Leukemia 14:826–829
Gong L, Liu M, Zeng T, Shi X, Yuan C, Andreasen PA, Huang M (2015) Crystal structure of the Michaelis complex between tissue-type plasminogen activator and plasminogen activators inhibitor-1. J Biol Chem 290:25795–25804. https://doi.org/10.1074/jbc.M115.677567
Guce AI, Clark NE, Salgado EN, Ivanen DR, Kulminskaya AA, Brumer H, Garman SC (2010) Catalytic mechanism of human alpha-galactosidase. J Biol Chem 285:3625–3632. https://doi.org/10.1074/jbc.M109.060145
Guce AI, Clark NE, Rogich JJ, Garman SC (2011) The molecular basis of pharmacological chaperoning in human α-galactosidase. Chem Biol 18:1521–1526. https://doi.org/10.1016/j.chembiol.2011.10.012
Han R-Z, Xu G-C, Dong J-J, Ni Y (2016) Arginine deiminase: recent advances in discovery, crystal structure, and protein engineering for improved properties as an anti-tumor drug. Appl Microbiol Biotechnol 100:4747–4760. https://doi.org/10.1007/s00253-016-7490-z
Harms E, Wehner A, Aung HP, Röhm KH (1991) A catalytic role for threonine-12 of E. coli asparaginase II as established by site-directed mutagenesis. FEBS Lett 285:55–58
Hassan MI, Waheed A, Grubb JH, Klei HE, Korolev S, Sly WS (2013) High resolution crystal structure of human β-glucuronidase reveals structural basis of lysosome targeting. PLoS One 8:e79687. https://doi.org/10.1371/journal.pone.0079687
Henningham A, Ericsson DJ, Langer K, Casey LW, Jovcevski B, Chhatwal GS, Aquilina JA, Batzloff MR, Kobe B, Walker MJ (2013) Structure-informed design of an enzymatically inactive vaccine component for group A Streptococcus. MBio 4:e00509-13–e00509-13. https://doi.org/10.1128/mBio.00509-13
Hill CH, Graham SC, Read RJ, Deane JE (2013) Structural snapshots illustrate the catalytic cycle of β-galactocerebrosidase, the defective enzyme in Krabbe disease. Proc Natl Acad Sci USA 110:20479–20484. https://doi.org/10.1073/pnas.1311990110
Hill CH, Viuff AH, Spratley SJ, Salamone S, Christensen SH, Read RJ, Moriarty NW, Jensen HH, Deane JE (2015) Azasugar inhibitors as pharmacological chaperones for Krabbe disease. Chem Sci 6:3075–3086. https://doi.org/10.1039/c5sc00754b
Hoogsteder PHJ, Kotz D, van Spiegel PI, Viechtbauer W, van Schayck OCP (2014) Efficacy of the nicotine vaccine 3′-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial. Addiction 109:1252–1259. https://doi.org/10.1111/add.12573
Jain S, Drendel WB, Chen Z-W, Mathews FS, Sly WS, Grubb JH (1996) Structure of human β-glucuronidase reveals candidate lysosomal targeting and active-site motifs. Nat Struct Mol Biol 3:375–381. https://doi.org/10.1038/nsb0496-375
Keyt BA, Paoni NF, Refino CJ, Berleau L, Nguyen H, Chow A, Lai J, Peña L, Pater C, Ogez J (1994) A faster-acting and more potent form of tissue plasminogen activator. Proc Natl Acad Sci USA 91:3670–3674
Khan FI, Shahbaaz M, Bisetty K, Waheed A, Sly WS, Ahmad F, Hassan MI (2016) Large scale analysis of the mutational landscape in β-glucuronidase: a major player of mucopolysaccharidosis type VII. Gene 576:36–44. https://doi.org/10.1016/j.gene.2015.09.062
Kishnani PS, Beckemeyer AA (2014) New therapeutic approaches for Pompe disease: enzyme replacement therapy and beyond. Pediatr Endocrinol Rev 12(Suppl 1):114–124
Kotzia GA, Labrou NE (2009) Engineering thermal stability of L-asparaginase by in vitro directed evolution. FEBS J 276:1750–1761. https://doi.org/10.1111/j.1742-4658.2009.06910.x
Kotzia GA, Lappa K, Labrou NE (2007) Tailoring structure-function properties of L-asparaginase: engineering resistance to trypsin cleavage. Biochem J 404:337–343. https://doi.org/10.1042/BJ20061708
Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M, Clark JF, Hamaoka T (2015) A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 5:11601. https://doi.org/10.1038/srep11601
Labrou NE, Papageorgiou AC, Avramis VI (2010) Structure-function relationships and clinical applications of L-asparaginases. Curr Med Chem 17:2183–2195
Lee WC, Kang D, Causevic E, Herdt AR, Eckman EA, Eckman CB (2010) Molecular characterization of mutations that cause globoid cell leukodystrophy and pharmacological rescue using small molecule chemical chaperones. J Neurosci 30:5489–5497. https://doi.org/10.1523/JNEUROSCI.6383-09.2010
Li L-Z, Xie T-H, Li H-J, Qing C, Zhang G-M, Sun M-S (2007) Enhancing the thermostability of Escherichia colil-asparaginase II by substitution with pro in predicted hydrogen-bonded turn structures. Enzym Microb Technol 41:523–527. https://doi.org/10.1016/j.enzmictec.2007.04.004
Lin Z, Jiang L, Yuan C, Jensen JK, Zhang X, Luo Z, Furie BC, Furie B, Andreasen PA, Huang M (2011) Structural basis for recognition of urokinase-type plasminogen activator by plasminogen activator inhibitor-1. J Biol Chem 286:7027–7032. https://doi.org/10.1074/jbc.M110.204537
Lourenço CM, Giugliani R (2014) Evaluation of galsulfase for the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Expert Opin Orphan Drugs 2:407–417. https://doi.org/10.1517/21678707.2014.885833
Maita N, Tsukimura T, Taniguchi T, Saito S, Ohno K, Taniguchi H, Sakuraba H (2013) Human α-L-iduronidase uses its own N-glycan as a substrate-binding and catalytic module. Proc Natl Acad Sci USA 110:14628–14633. https://doi.org/10.1073/pnas.1306939110
Marr RA, Hafez DM (2014) Amyloid-beta and Alzheimer’s disease: the role of neprilysin-2 in amyloid-beta clearance. Front Aging Neurosci 6:187. https://doi.org/10.3389/fnagi.2014.00187
Miners JS, Barua N, Kehoe PG, Gill S, Love S (2011) Aβ-degrading enzymes: potential for treatment of Alzheimer disease. J Neuropathol Exp Neurol 70:944–959. https://doi.org/10.1097/NEN.0b013e3182345e46
Moffitt MC, Louie GV, Bowman ME, Pence J, Noel JP, Moore BS (2007) Discovery of two cyanobacterial phenylalanine ammonia lyases: kinetic and structural characterization. Biochemistry 46:1004–1012. https://doi.org/10.1021/bi061774g
Mohamed FE, Al-Gazali L, Al-Jasmi F, Ali BR (2017) Pharmaceutical chaperones and proteostasis regulators in the therapy of lysosomal storage disorders: current perspective and future promises. Front Pharmacol 8:448. https://doi.org/10.3389/fphar.2017.00448
Montaño AM, Lock-Hock N, Steiner RD, Graham BH, Szlago M, Greenstein R, Pineda M, Gonzalez-Meneses A, Çoker M, Bartholomew D, Sands MS, Wang R, Giugliani R, Macaya A, Pastores G, Ketko AK, Ezgü F, Tanaka A, Arash L, Beck M, Falk RE, Bhattacharya K, Franco J, White KK, Mitchell GA, Cimbalistiene L, Holtz M, Sly WS (2016) Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet 53:403–418. https://doi.org/10.1136/jmedgenet-2015-103322
Nalivaeva NN, Beckett C, Belyaev ND, Turner AJ (2012) Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer’s disease? J Neurochem 120:167–185. https://doi.org/10.1111/j.1471-4159.2011.07510.x
Naz H, Islam A, Waheed A, Sly WS, Ahmad F, Hassan I (2013) Human β-glucuronidase: structure, function, and application in enzyme replacement therapy. Rejuvenation Res 16:352–363. https://doi.org/10.1089/rej.2013.1407
Ni Y, Schwaneberg U, Sun Z-H (2008) Arginine deiminase, a potential anti-tumor drug. Cancer Lett 261:1–11. https://doi.org/10.1016/j.canlet.2007.11.038
Ortlund E, Lacount MW, Lewinski K, Lebioda L (2000) Reactions of pseudomonas 7A glutaminase-asparaginase with diazo analogues of glutamine and asparagine result in unexpected covalent inhibitions and suggests an unusual catalytic triad Thr-Tyr-Glu. Biochemistry 39:1199–1204
Osellame LD, Duchen MR (2013) Defective quality control mechanisms and accumulation of damaged mitochondria link Gaucher and Parkinson diseases. Autophagy 9:1633–1635. https://doi.org/10.4161/auto.25878
Palm G, Lubkowski J, Derst C, Schleper S (1996) A covalently bound catalytic intermediate in Escherichia coli asparaginase: crystal structure of a Thr-89-Val mutant. FEBS Lett 390:211–216
Pan R, Zhang Z-J, He R-Q (2010) Earthworm protease. Appl Environ Soil 2010:13. https://doi.org/10.1155/2010/294258
Papageorgiou AC, Posypanova GA, Andersson CS, Sokolov NN, Krasotkina J (2008) Structural and functional insights into Erwinia carotovora L-asparaginase. FEBS J 275:4306–4316. https://doi.org/10.1111/j.1742-4658.2008.06574.x
Parenti G, Fecarotta S, la Marca G, Rossi B, Ascione S, Donati MA, Morandi LO, Ravaglia S, Pichiecchio A, Ombrone D, Sacchini M, Pasanisi MB, De Filippi P, Danesino C, Casa Della R, Romano A, Mollica C, Rosa M, Agovino T, Nusco E, Porto C, Andria G (2014) A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy. Mol Ther 22:2004–2012. https://doi.org/10.1038/mt.2014.138
Parsiegla G, Noguere C, Santell L, Lazarus RA, Bourne Y (2012) The structure of human DNase I bound to magnesium and phosphate ions points to a catalytic mechanism common to members of the DNase I-like superfamily. Biochemistry 51:10250–10258. https://doi.org/10.1021/bi300873f
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera – a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612. https://doi.org/10.1002/jcc.20084
Pol-Fachin L, Siebert M, Verli H, Saraiva-Pereira ML (2016) Glycosylation is crucial for a proper catalytic site organization in human glucocerebrosidase. Glycoconj J 33:237–244. https://doi.org/10.1007/s10719-016-9661-7
Pretzer D, Schulteis B, Vander Velde DG, Smith CD, Mitchell JW, Manning MC (1992) Effect of zinc binding on the structure and stability of fibrolase, a fibrinolytic protein from snake venom. Pharm Res 9:870–877. https://doi.org/10.1023/A:1015840613799
Ran C, Brodin L, Forsgren L, Westerlund M, Ramezani M, Gellhaar S, Xiang F, Fardell C, Nissbrandt H, Söderkvist P, Puschmann A, Ygland E, Olson L, Willows T, Johansson A, Sydow O, Wirdefeldt K, Galter D, Svenningsson P, Belin AC (2016) Strong association between glucocerebrosidase mutations and Parkinson’s disease in Sweden. Neurobiol Aging 45:212.e5–212.e11. https://doi.org/10.1016/j.neurobiolaging.2016.04.022
Rivera-Colón Y, Schutsky EK, Kita AZ, Garman SC (2012) The structure of human GALNS reveals the molecular basis for mucopolysaccharidosis IV A. J Mol Biol 423:736–751. https://doi.org/10.1016/j.jmb.2012.08.020
Roig-Zamboni V, Cobucci-Ponzano B, Iacono R, Ferrara MC, Germany S, Bourne Y, Parenti G, Moracci M, Sulzenbacher G (2017) Structure of human lysosomal acid α-glucosidase-a guide for the treatment of Pompe disease. Nat Commun 8:1111. https://doi.org/10.1038/s41467-017-01263-3
Saito S, Ohno K, Maita N, Sakuraba H (2014) Structural and clinical implications of amino acid substitutions in α-L-iduronidase: insight into the basis of mucopolysaccharidosis type I. Mol Genet Metab 111:107–112. https://doi.org/10.1016/j.ymgme.2013.10.005
Semba CP, Sugimoto K, Razavi MK, Society of Cardiovascular and Interventional Radiology (SCVIR) (2001) Alteplase and tenecteplase: applications in the peripheral circulation. Tech Vasc Interv Radiol 4:99–106
Sharma SK, Bagshawe KD (2017) Antibody Directed Enzyme Prodrug Therapy (ADEPT): trials and tribulations. Adv Drug Deliv Rev 118:2–7. https://doi.org/10.1016/j.addr.2017.09.009
Sidhu NS, Schreiber K, Propper K, Becker S, Uson I, Sheldrick GM, Gartner J, Kratzner R, Steinfeld R (2014) Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA. Acta Cryst D70:1321–1335. 1–15. https://doi.org/10.1107/S1399004714002739
Spratley SJ, Deane JE (2016) New therapeutic approaches for Krabbe disease: the potential of pharmacological chaperones. J Neurosci Res 94:1203–1219. https://doi.org/10.1002/jnr.23762
Tang Y, Liang D, Jiang T, Zhang J, Gui L, Chang W (2002) Crystal structure of earthworm fibrinolytic enzyme component a: revealing the structural determinants of its dual fibrinolytic activity. J Mol Biol 321:57–68
Tararina MA, Janda KD, Allen KN (2016) Structural analysis provides mechanistic insight into nicotine oxidoreductase from Pseudomonas putida. Biochemistry 55:6595–6598. https://doi.org/10.1021/acs.biochem.6b00963
Thomas J, Levy H, Amato S, Vockley J, Zori R, Dimmock D, Harding CO, Bilder DA, Weng HH, Olbertz J, Merilainen M, Jiang J, Larimore K, Gupta S, Gu Z, Northrup H (2018) Pegvaliase for the treatment of phenylketonuria: results of a long-term phase 3 clinical trial program (PRISM). Mol Genet Metab 124:27–38. https://doi.org/10.1016/j.ymgme.2018.03.006
Tomatsu S, Montaño AM, Dung VC, Ohashi A, Oikawa H, Oguma T, Orii T, Barrera L, Sly WS (2010) Enhancement of drug delivery: enzyme-replacement therapy for murine Morquio A syndrome. Mol Ther 18:1094–1102. https://doi.org/10.1038/mt.2010.32
van den Berg H (2011) Asparaginase revisited. Leuk Lymphoma 52:168–178. https://doi.org/10.3109/10428194.2010.537796
Van Hove JL, Yang HW, Wu JY, Brady RO, Chen YT (1996) High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease. Proc Natl Acad Sci USA 93:65–70
Viuff AH, Jensen HH (2016) Synthesis and evaluation of N-alkylated analogues of aza-galacto-fagomine – potential pharmacological chaperones for Krabbe disease. Org Biomol Chem 14:8545–8556. https://doi.org/10.1039/c6ob01309k
Wang F, Wang C, Li M, Zhang JP, Gui LL, An X-M, Chang WR (2005a) Crystal structure of earthworm fibrinolytic enzyme component B: a novel, glycosylated two-chained trypsin. J Mol Biol 348:671–685. https://doi.org/10.1016/j.jmb.2005.02.055
Wang L, Gamez A, Sarkissian CN, Straub M, Patch MG, Han GW, Striepeke S, Fitzpatrick P, Scriver CR, Stevens RC (2005b) Structure-based chemical modification strategy for enzyme replacement treatment of phenylketonuria. Mol Genet Metab 86:134–140. https://doi.org/10.1016/j.ymgme.2005.05.012
Wang L, Gamez A, Archer H, Abola EE, Sarkissian CN, Fitzpatrick P, Wendt D, Zhang Y, Vellard M, Bliesath J, Bell SM, Lemontt JF, Scriver CR, Stevens RC (2008) Structural and biochemical characterization of the therapeutic Anabaena variabilis phenylalanine ammonia lyase. J Mol Biol 380:623–635. https://doi.org/10.1016/j.jmb.2008.05.025
Wang KY, Tull L, Cooper E, Wang N, Liu D (2013) Recombinant protein production of earthworm lumbrokinase for potential antithrombotic application. Evid Based Complement Alternat Med 2013:783971–783978. https://doi.org/10.1155/2013/783971
Webster CI, Burrell M, Olsson L-L, Fowler SB, Digby S, Sandercock A, Snijder A, Tebbe J, Haupts U, Grudzinska J, Jermutus L, Andersson C (2014) Engineering neprilysin activity and specificity to create a novel therapeutic for Alzheimer’s disease. PLoS One 9:e104001. https://doi.org/10.1371/journal.pone.0104001
Xue S, Kallupi M, Zhou B, Smith LC, Miranda PO, George O, Janda KD (2018) An enzymatic advance in nicotine cessation therapy. Chem Commun (Camb) 30:217. https://doi.org/10.1039/c7cc09134f
Yanagisawa Y, Chatake T, Chiba-Kamoshida K, Naito S, Ohsugi T, Sumi H, Yasuda I, Morimoto Y (2010) Purification, crystallization and preliminary X-ray diffraction experiment of nattokinase from Bacillus subtilis natto. Acta Crystallogr Sect F Struct Biol Cryst Commun 66:1670–1673. https://doi.org/10.1107/S1744309110043137
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Papageorgiou, A.C. (2019). X-Ray Crystallography in Structure-Function Characterization of Therapeutic Enzymes. In: Labrou, N. (eds) Therapeutic Enzymes: Function and Clinical Implications. Advances in Experimental Medicine and Biology, vol 1148. Springer, Singapore. https://doi.org/10.1007/978-981-13-7709-9_4
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