M J Blackman

Summary

Affiliation: National Institute for Medical Research
Country: UK

Publications

  1. ncbi request reprint Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes
    Sharon Yeoh
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Cell 131:1072-83. 2007
  2. pmc Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite
    Rebecca A O'Donnell
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, England, UK
    J Cell Biol 174:1023-33. 2006
  3. pmc An inhibitory antibody blocks interactions between components of the malarial invasion machinery
    Christine R Collins
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London, United Kingdom
    PLoS Pathog 5:e1000273. 2009
  4. pmc A multifunctional serine protease primes the malaria parasite for red blood cell invasion
    Konstantinos Koussis
    Division of Parasitology, National Institute for Medical Research, London, UK
    EMBO J 28:725-35. 2009
  5. pmc Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies
    Anna Olivieri
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom
    PLoS Pathog 7:e1002448. 2011
  6. pmc Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte
    Andrea Ruecker
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 287:37949-63. 2012
  7. pmc Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth
    Matthew A Child
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Microbiol 78:187-202. 2010
  8. pmc Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress
    Christine R Collins
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom
    PLoS Pathog 9:e1003344. 2013
  9. pmc Extracellular ATP triggers proteolysis and cytosolic Ca²⁺ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites
    Laura Nogueira Cruz
    Department of Physiology, Instituto de Biociencias, Universidade de Sao Paulo, Rua do Matao, Butantan, 05508 900 Sao Paulo, SP Brazil
    Malar J 11:69. 2012
  10. pmc Plasmodium subtilisin-like protease 1 (SUB1): insights into the active-site structure, specificity and function of a pan-malaria drug target
    Chrislaine Withers-Martinez
    Division of Parasitology, MRC National Institute for Medical Research NIMR, Mill Hill, London NW7 1AA, UK
    Int J Parasitol 42:597-612. 2012

Collaborators

Detail Information

Publications48

  1. ncbi request reprint Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes
    Sharon Yeoh
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Cell 131:1072-83. 2007
    ..Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte...
  2. pmc Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite
    Rebecca A O'Donnell
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, England, UK
    J Cell Biol 174:1023-33. 2006
    ..Mutations within the EBA-175 TMD that abolish cleavage by PfROM4 prevent parasite growth. Our results identify a crucial role for intramembrane proteolysis in the life cycle of this pathogen...
  3. pmc An inhibitory antibody blocks interactions between components of the malarial invasion machinery
    Christine R Collins
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London, United Kingdom
    PLoS Pathog 5:e1000273. 2009
    ..We propose that mAb 4G2 inhibits invasion by preventing PfAMA1 from interacting with other components of the invasion complex. Our findings should aid the rational design of subunit malaria vaccines based on PfAMA1...
  4. pmc A multifunctional serine protease primes the malaria parasite for red blood cell invasion
    Konstantinos Koussis
    Division of Parasitology, National Institute for Medical Research, London, UK
    EMBO J 28:725-35. 2009
    ..We propose that PfSUB1 is a multifunctional processing protease with an essential role in both egress of the malaria merozoite and remodelling of its surface in preparation for erythrocyte invasion...
  5. pmc Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies
    Anna Olivieri
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom
    PLoS Pathog 7:e1002448. 2011
    ..Drugs that inhibit PfSUB2 activity should block parasite replication and may also enhance the efficacy of vaccines based on AMA1 and other merozoite surface proteins...
  6. pmc Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte
    Andrea Ruecker
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 287:37949-63. 2012
    ..Our observations reveal a proteolytic activation step in the malarial PV that may be required for release of the parasite from its host erythrocyte...
  7. pmc Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth
    Matthew A Child
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Microbiol 78:187-202. 2010
    ..Our findings show that correct spatiotemporal regulation of MSP1 maturation is crucial for the function of the protein and for maintenance of the parasite asexual blood-stage life cycle...
  8. pmc Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress
    Christine R Collins
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom
    PLoS Pathog 9:e1003344. 2013
    ....
  9. pmc Extracellular ATP triggers proteolysis and cytosolic Ca²⁺ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites
    Laura Nogueira Cruz
    Department of Physiology, Instituto de Biociencias, Universidade de Sao Paulo, Rua do Matao, Butantan, 05508 900 Sao Paulo, SP Brazil
    Malar J 11:69. 2012
    ..Plasmodium has a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host...
  10. pmc Plasmodium subtilisin-like protease 1 (SUB1): insights into the active-site structure, specificity and function of a pan-malaria drug target
    Chrislaine Withers-Martinez
    Division of Parasitology, MRC National Institute for Medical Research NIMR, Mill Hill, London NW7 1AA, UK
    Int J Parasitol 42:597-612. 2012
    ..Our findings demonstrate that it should be possible to develop 'pan-reactive' drug-like compounds that inhibit SUB1 in all three major human malaria pathogens, enabling production of broad-spectrum antimalarial drugs targeting SUB1...
  11. pmc Antibodies against multiple merozoite surface antigens of the human malaria parasite Plasmodium falciparum inhibit parasite maturation and red blood cell invasion
    Ute Woehlbier
    Zentrum für Molekulare Biologie ZMBH, University of Heidelberg, Im Neuenheimer Feld 282, D 69120 Heidelberg, Germany
    Malar J 9:77. 2010
    ..Components of the MSP-1/6/7 complex and AMA-1 are presently under development as malaria vaccines...
  12. ncbi request reprint Structural and biochemical characterization of a fluorogenic rhodamine-labeled malarial protease substrate
    Michael J Blackman
    National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, U K
    Biochemistry 41:12244-52. 2002
    ..These data also indicate that the rhodamine dimers fluoresce and that the associated lifetimes are subnanosecond...
  13. ncbi request reprint Apical organelles of Apicomplexa: biology and isolation by subcellular fractionation
    M J Blackman
    Division of Parasitology, National Institute for Medical Research, Mill Hill, NW7 1AA, London, UK
    Mol Biochem Parasitol 117:11-25. 2001
    ..The merits and limitations of these different types of approach are discussed, and the importance of cell fractionation methods in characterising apical organelle proteins is stressed...
  14. ncbi request reprint Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic targets
    M J Blackman
    Division of Parasitology, National Institute for Medical Research, Ridgeway, Mill Hill, London NW7 1AA, U K
    Curr Drug Targets 1:59-83. 2000
    ..This review details recent advances in the identification of these proteases, describes current understanding of their activation and functional role, and discusses their potential as targets for protease inhibitor-based drugs...
  15. ncbi request reprint Proteases in host cell invasion by the malaria parasite
    Michael J Blackman
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Cell Microbiol 6:893-903. 2004
    ..This review summarizes the evidence for this, discusses selected well-described proteolytic modifications linked to invasion, and describes recent progress towards identifying the proteases involved...
  16. ncbi request reprint A subtilisin-like protein in secretory organelles of Plasmodium falciparum merozoites
    M J Blackman
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 273:23398-409. 1998
    ..The subcellular location and timing of secretion of p47 suggest that it is likely to play a role in erythrocyte invasion. PfSUB-1 is a new potential target for antimalarial drug development...
  17. pmc Malarial proteases and host cell egress: an 'emerging' cascade
    Michael J Blackman
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Cell Microbiol 10:1925-34. 2008
    ..These findings are discussed in the context of the potential for development of new chemotherapeutics targeting this stage in the parasite's life cycle...
  18. ncbi request reprint Plasmodium knowlesi: secondary processing of the malaria merozoite surface protein-1
    M J Blackman
    Division of Parasitology, National Institute for Medical Research, London, United Kingdom
    Exp Parasitol 83:229-39. 1996
    ..Successful invasion is therefore associated with complete shedding of MSP-1(33) from the merozoite surface. The nucleotide sequence of the 3' domain of the P. knowlesi MSP-1 gene is also presented...
  19. ncbi request reprint Proteolytic processing and primary structure of Plasmodium falciparum apical membrane antigen-1
    S A Howell
    Division of Protein Structure and the Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 276:31311-20. 2001
    ..As a result, the bulk of the ectodomain is shed from the parasite surface in the form of two soluble fragments of 44 and 48 kDa. PfAMA-1 is not detectably modified by the addition of N-linked oligosaccharides...
  20. ncbi request reprint Distinct mechanisms govern proteolytic shedding of a key invasion protein in apicomplexan pathogens
    Steven A Howell
    Department of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Microbiol 57:1342-56. 2005
    ..This work reveals unexpected differences in the manner in which Plasmodium and Toxoplasma shed AMA1 from the surface of invasive zoites, and demonstrates the presence at the malaria merozoite surface of a rhomboid-like protease...
  21. ncbi request reprint Malarial EBA-175 region VI crystallographic structure reveals a KIX-like binding interface
    Chrislaine Withers-Martinez
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    J Mol Biol 375:773-81. 2008
    ....
  22. ncbi request reprint Fine mapping of an epitope recognized by an invasion-inhibitory monoclonal antibody on the malaria vaccine candidate apical membrane antigen 1
    Christine R Collins
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 282:7431-41. 2007
    ..Our results will aid in the design of subunit vaccines designed to generate a broadly effective, focused anti-PfAMA1 protective immune response and may help elucidate the function of PfAMA1...
  23. ncbi request reprint Expression of recombinant Plasmodium falciparum subtilisin-like protease-1 in insect cells. Characterization, comparison with the parasite protease, and homology modeling
    Chrislaine Withers-Martinez
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 277:29698-709. 2002
    ..A predicted highly polar S1 pocket and a hydrophobic S4 subsite are in broad agreement with the experimentally determined substrate specificity...
  24. ncbi request reprint A single malaria merozoite serine protease mediates shedding of multiple surface proteins by juxtamembrane cleavage
    Steven A Howell
    Division of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 278:23890-8. 2003
    ..Our results indicate the presence on the merozoite surface of a multifunctional serine sheddase with a broad substrate specificity. We further demonstrate that translocation and shedding of PfAMA-1 is an actin-independent process...
  25. ncbi request reprint Functional characterization of the propeptide of Plasmodium falciparum subtilisin-like protease-1
    Letitia Jean
    Parasitology and Physical Biochemistry, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 278:28572-9. 2003
    ..These studies provide new insights into the function of the propeptide in PfSUB-1 activation and shed light on the structural requirements for interaction with the catalytic domain...
  26. ncbi request reprint Suramin and suramin analogues inhibit merozoite surface protein-1 secondary processing and erythrocyte invasion by the malaria parasite Plasmodium falciparum
    Suzanne L Fleck
    Medical Research Council Technology, 1 3 Burtonhole Lane, Mill Hill, London NW7 1AD, United Kingdom
    J Biol Chem 278:47670-7. 2003
    ..The results indicate that enzymatic events during invasion are suitable targets for drug development and validate the novel concept of an inhibitor binding to a macromolecular substrate to prevent its proteolysis by a protease...
  27. ncbi request reprint Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria
    A A Holder
    Division of Parasitology, National Institute for Medical Research, London, UK
    Parassitologia 41:409-14. 1999
    ..This mechanism has a number of implications for the study of protective immunity and the development of malaria vaccines, emphasising the need for appropriate functional assays and careful design of the antigen...
  28. ncbi request reprint Unique insertions within Plasmodium falciparum subtilisin-like protease-1 are crucial for enzyme maturation and activity
    Letitia Jean
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Biochem Parasitol 144:187-97. 2005
    ....
  29. ncbi request reprint Roles of proteases during invasion and egress by Plasmodium and Toxoplasma
    Timothy J Dowse
    Department of Biological Sciences, Imperial College, London, UK
    Subcell Biochem 47:121-39. 2008
    ....
  30. ncbi request reprint The role of malaria merozoite proteases in red blood cell invasion
    Rebecca A O'Donnell
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK
    Curr Opin Microbiol 8:422-7. 2005
    ..This supports their role in capping proteolysis. Proteases involved in invasion constitute potential targets for the development of new protease inhibitor-based drugs...
  31. ncbi request reprint Subtilisin-like proteases of the malaria parasite
    Chrislaine Withers-Martinez
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Microbiol 53:55-63. 2004
    ..They may have potential as novel drug targets. Here, we review progress in our understanding of the maturation, specificity, structure and function of these Plasmodium subtilases...
  32. ncbi request reprint A role for poly(dA)poly(dT) tracts in directing activity of the Plasmodium falciparum calmodulin gene promoter
    Hannah E J Polson
    Division of Parasitology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Mol Biochem Parasitol 141:179-89. 2005
    ..falciparum transcription-initiation complex has a low degree of sequence-specificity for the sites of initiation but preferentially acts downstream of long poly(dA)poly(dT) tracts...
  33. pmc Atomic resolution insight into host cell recognition by Toxoplasma gondii
    Tharin M A Blumenschein
    Division of Molecular Biosciences, Imperial College London, London, UK
    EMBO J 26:2808-20. 2007
    ..Our work uncovers new features of parasite-receptor interactions at the early stages of host cell invasion, which will assist the design of new therapeutic strategies...
  34. pmc Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease
    Natalie C Silmon de Monerri
    Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    Infect Immun 79:1086-97. 2011
    ..Our findings imply multiple roles for PfSUB1 in the parasite life cycle, further supporting the case for considering the protease as a potential new antimalarial drug target...
  35. ncbi request reprint Potent inhibitors of the Plasmodium falciparum enzymes plasmepsin I and II devoid of cathepsin D inhibitory activity
    Karolina Ersmark
    Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, SE 751 23 Uppsala, Sweden
    J Med Chem 47:110-22. 2004
    ..To the best of our knowledge, these plasmepsin inhibitors represent the most selective reported to date and constitute promising lead compounds for further optimization...
  36. pmc High-level expression of the malaria blood-stage vaccine candidate Plasmodium falciparum apical membrane antigen 1 and induction of antibodies that inhibit erythrocyte invasion
    Clemens H M Kocken
    Department of Parasitology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands
    Infect Immun 70:4471-6. 2002
    ..falciparum by immunofluorescence. In addition, purified immunoglobulin G from immunized animals strongly inhibited invasion of red blood cells by homologous and, to a somewhat lesser extent, heterologous P. falciparum...
  37. ncbi request reprint Crystal structure of the malaria vaccine candidate apical membrane antigen 1
    Juan Carlos Pizarro
    Unité d Immunologie Structurale, Centre National de la Recherche Scientifique, URA 2185, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France
    Science 308:408-11. 2005
    ..These results are likely to aid vaccine and drug design...
  38. ncbi request reprint TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase
    Steven A Miller
    Departments of Medicine and of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx NY 10461, USA
    Mol Microbiol 49:883-94. 2003
    ..Processing of secretory organelle contents appears to be ubiquitous among the Apicomplexa. As subtilases are present in genomes of all the Apicomplexa sequenced to date, subtilases may represent a novel chemotherapeutic target...
  39. ncbi request reprint Plasmodium falciparum apical membrane antigen 1 (PfAMA-1) is translocated within micronemes along subpellicular microtubules during merozoite development
    Lawrence H Bannister
    Department of Anatomy, Cell and Human Biology, Guy s, King s and St Thomas School of Biomedical Science, Guy s Hospital, London SE1 1UL, UK
    J Cell Sci 116:3825-34. 2003
    ..This result confirms that PfAMA-1 is a micronemal protein, and indicates that within the microneme it is located near or inserted into this organelle's boundary membrane...
  40. ncbi request reprint Structural comparison of apical membrane antigen 1 orthologues and paralogues in apicomplexan parasites
    Marie Laure Chesne-Seck
    Unité d Immunologie Structurale, CNRS URA 2185, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, France
    Mol Biochem Parasitol 144:55-67. 2005
    ....
  41. ncbi request reprint A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites
    Olivier Silvie
    INSERM U511, Immunobiologie Cellulaire et Moleculaire des Infections Parasitaires, Centre Hospitalo Universitaire Pitie Salpetriere, Universite Pierre et Marie Curie, 75013 Paris, France
    J Biol Chem 279:9490-6. 2004
    ....
  42. ncbi request reprint Proteomic analysis of cleavage events reveals a dynamic two-step mechanism for proteolysis of a key parasite adhesive complex
    Xing W Zhou
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Mol Cell Proteomics 3:565-76. 2004
    ..Our data support a novel two-step proteolysis model that includes primary processing of the MIC2/M2AP complex followed by secondary cleavage to shed the complex from the parasite surface during the final steps of invasion...
  43. ncbi request reprint RNAi in protozoan parasites: what hope for the Apicomplexa?
    Michael J Blackman
    Protist 154:177-80. 2003
  44. ncbi request reprint Design and synthesis of potent inhibitors of plasmepsin I and II: X-ray crystal structure of inhibitor in complex with plasmepsin II
    Per Ola Johansson
    Department of Chemistry, Linkoping University, S 581 83 Linkoping, Sweden
    J Med Chem 48:4400-9. 2005
    ..The design was partially guided by the X-ray crystal structure disclosed herein of the previously synthesized inhibitor 1 in complex with plasmepsin II...
  45. ncbi request reprint Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations
    Karolina Ersmark
    Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, 751 23 Uppsala, Sweden
    J Med Chem 48:6090-106. 2005
    ..One compound, lacking amide bonds, was found to be Plm IV selective and very potent, with a Ki value of 35 nM...
  46. ncbi request reprint A conserved subtilisin protease identified in Babesia divergens merozoites
    Estrella Montero
    Department of Molecular Parasitology, Lindsley Kimball Research Institute, New York Blood Center, New York, New York 10021, USA
    J Biol Chem 281:35717-26. 2006
    ....
  47. ncbi request reprint A new release on life: emerging concepts in proteolysis and parasite invasion
    Vern B Carruthers
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Mol Microbiol 55:1617-30. 2005
    ..The sequential proteolytic events associated with invasion by pathogenic protozoa may represent vulnerable pathways for the future development of synergistic anti-protozoal therapies...
  48. ncbi request reprint Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II. Use of solid-phase synthesis to explore novel statine motifs
    Per Ola Johansson
    Department of Chemistry, Linkoping University, S 581 83 Linkoping, Sweden
    J Med Chem 47:3353-66. 2004
    ..Several inhibitors have been identified that exhibit Ki values between 0.5 and 74 nM for both Plm I and II. Some of these inhibitors also show excellent selectivity vs cathepsin D...