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      Maggot Kinase and Natural Thrombolytic Proteins

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          Abstract

          Thrombolytic enzymes constitute a class of proteases with antithrombotic functions. Derived from natural products and abundant in nature, certain thrombolytic enzymes, such as urokinase, earthworm kinase, and streptokinase, have been widely used in the clinical treatment of vascular embolic diseases. Fly maggots, characterized by their easy growth and low cost, are a traditional Chinese medicine recorded in the Compendium of Materia Medica. These maggots can also be used as raw material for the extraction and preparation of thrombolytic enzymes (maggot kinase). In this review, we assembled global research reports on natural thrombolytic enzymes through a literature search and reviewed the functions and structures of natural thrombolytic enzymes to provide a reference for natural thrombophilic drug screening and development.

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          Most cited references142

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          Snake venom metalloproteinases.

          Recent proteomic analyses of snake venoms show that metalloproteinases represent major components in most of the Crotalid and Viperid venoms. In this chapter we discuss the multiple activities of the SVMPs. In addition to hemorrhagic activity, members of the SVMP family also have fibrin(ogen)olytic activity, act as prothrombin activators, activate blood coagulation factor X, possess apoptotic activity, inhibit platelet aggregation, are pro-inflammatory and inactivate blood serine proteinase inhibitors. Clearly the SVMPs have multiple functions in addition to their well-known hemorrhagic activity. The realization that there are structural variations in the SVMPs and the early studies that led to their classification represents an important event in our understanding of the structural forms of the SVMPs. The SVMPs were subdivided into the P-I, P-II and P-III protein classes. The noticeable characteristic that distinguished the different classes was their size (molecular weight) differences and domain structure: Class I (P-I), the small SVMPs, have molecular masses of 20-30 kDa, contain only a pro domain and the proteinase domain; Class II (P-II), the medium size SVMPs, molecular masses of 30-60 kDa, contain the pro domain, proteinase domain and disintegrin domain; Class III (P-III), the large SVMPs, have molecular masses of 60-100 kDa, contain pro, proteinase, disintegrin-like and cysteine-rich domain structure. Another significant advance in the SVMP field was the characterization of the crystal structure of the first P-I class SVMP. The structures of other P-I SVMPs soon followed and the structures of P-III SVMPs have also been determined. The active site of the metalloproteinase domain has a consensus HEXXHXXGXXHD sequence and a Met-turn. The "Met-turn" structure contains a conserved Met residue that forms a hydrophobic basement for the three zinc-binding histidines in the consensus sequence. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet.

            A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto, which is a typical soybean food eaten in Japan. The average activity was calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic enzyme, named nattokinase, was easily extracted with saline. The mol. wt and pI were about 20,000 and 8.6, respectively. Nattokinase not only digested fibrin but also the plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251), which was more sensitive to the enzyme than other substrates tried. Diisopropyl fluorophosphate and 2,2,2-trichloro-1-hydroxyethyl-o,o-dimethylphosphate strongly inhibited this fibrinolytic enzyme.
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              Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases

              Cardiovascular disease (CVD) is the leading cause of death in the world and our approach to the control and management of CVD mortality is limited. Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. This review covers the major pharmacologic effects of NK with a focus on its clinical relevance to CVD. It outlines the advantages of NK and the outstanding issues pertaining to NK pharmacokinetics. Available evidence suggests that NK is a unique natural compound that possesses several key cardiovascular beneficial effects for patients with CVD and is therefore an ideal drug candidate for the prevention and treatment of CVD. Nattokinase is a promising alternative in the management of CVD.
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                Author and article information

                Journal
                ACS Omega
                ACS Omega
                ao
                acsodf
                ACS Omega
                American Chemical Society
                2470-1343
                02 May 2024
                21 May 2024
                : 9
                : 20
                : 21768-21779
                Affiliations
                []Key Laboratory for Northern Urban Agriculture of Ministry of Agriculture and Rural Affairs of China, Beijing University of Agriculture , Beijing 102206, PR China
                []Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing University of Agriculture , Beijing 102206, PR China
                Author notes
                [* ]Email: lqma@ 123456bua.edu.cn . Phone number: +86-10-80797305. Fax number: +86-10-80797305.
                Author information
                https://orcid.org/0000-0002-2036-0826
                https://orcid.org/0000-0002-5578-6958
                Article
                10.1021/acsomega.4c01663
                11112594
                74a8fd3c-a5ce-49c5-a23e-e3b5d5446bc1
                © 2024 The Authors. Published by American Chemical Society

                Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 20 February 2024
                : 25 April 2024
                : 22 April 2024
                Funding
                Funded by: Ministry of Agriculture and Rural Affairs of the People''s Republic of China, doi 10.13039/501100011798;
                Award ID: BUAPSP202201
                Categories
                Review
                Custom metadata
                ao4c01663
                ao4c01663

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