PDBsum entry 1n1i

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Cell adhesion PDB id
Protein chains
91 a.a. *
IMD ×2
Waters ×306
* Residue conservation analysis
PDB id:
Name: Cell adhesion
Title: The structure of msp-1(19) from plasmodium knowlesi
Structure: Merozoite surface protein-1. Chain: a, b, c, d. Fragment: c-terminal egf-like domains. Engineered: yes
Source: Plasmodium knowlesi strain h. Organism_taxid: 5851. Strain: malayan h. Gene: msp1. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
2.40Å     R-factor:   0.234     R-free:   0.264
Authors: S.C.Garman,W.N.Simcoke,A.W.Stowers,D.N.Garboczi
Key ref:
S.C.Garman et al. (2003). Structure of the C-terminal domains of merozoite surface protein-1 from Plasmodium knowlesi reveals a novel histidine binding site. J Biol Chem, 278, 7264-7269. PubMed id: 12493733 DOI: 10.1074/jbc.M210716200
17-Oct-02     Release date:   25-Feb-03    
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Protein chains
Pfam   ArchSchema ?
Q9GSQ9  (Q9GSQ9_PLAKN) -  Merozoite surface protein 1 (Fragment)
328 a.a.
91 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1074/jbc.M210716200 J Biol Chem 278:7264-7269 (2003)
PubMed id: 12493733  
Structure of the C-terminal domains of merozoite surface protein-1 from Plasmodium knowlesi reveals a novel histidine binding site.
S.C.Garman, W.N.Simcoke, A.W.Stowers, D.N.Garboczi.
The protozoan parasite Plasmodium causes malaria, with hundreds of millions of cases recorded annually. Protection against malaria infection can be conferred by antibodies against merozoite surface protein (MSP)-1, making it an attractive vaccine candidate. Here we present the structure of the C-terminal domains of MSP-1 (known as MSP-1(19)) from Plasmodium knowlesi. The structure reveals two tightly packed epidermal growth factor-like domains oriented head to tail. In domain 1, the molecule displays a histidine binding site formed primarily by a highly conserved tryptophan. The protein carries a pronounced overall negative charge primarily due to the large number of acidic groups in domain 2. To map protein binding surfaces on MSP-1(19), we have analyzed the crystal contacts in five different crystal environments, revealing that domain 1 is highly preferred in protein-protein interactions. A comparison of MSP-1(19) structures from P. knowlesi, P. cynomolgi, and P. falciparum shows that, although the overall protein folds are similar, the molecules show significant differences in charge distribution. We propose the histidine binding site in domain 1 as a target for inhibitors of protein binding to MSP-1, which might prevent invasion of the merozoite into red blood cells.
  Selected figure(s)  
Figure 3.
Fig. 3. MSP-1[19] in crystal contacts and across species. a, the P. knowlesi MSP-1[19] molecular surface is shown, colored by the number of crystal contacts each residue makes, using the four molecules in the P. knowlesi asymmetric unit and the one molecule in the P. cynomolgi asymmetric unit. The surface has a color gradient from 0 (white; no contacts in any of the five molecules) to 5 (blue; contacts in each of the five molecules) crystal contacts/residue. The histidine binding site is circled in red. b, carbon traces of MSP-1[19] from P. knowlesi, P. cynomolgi, and P. falciparum are superimposed. The four copies of P. knowlesi MSP-1[19] are colored yellow, green, blue, and red; the P. cynomolgi MSP-1[19] is colored magenta; and the P. falciparum MSP-1[19] NMR structure is colored white. Non-native residues from the purification epitope of P. knowlesi are included at the bottom of domain 2.
Figure 4.
Fig. 4. Electrostatic potential and hydrophobicity. a, the amino acid sequences from the crystals of MSP-1[19] from P. knowlesi, P. cynomolgi, and P. falciparum. Cysteines are highlighted in yellow. b d, surface representations of MSP-1[19] from three Plasmodium species are shown, colored by electrostatic potential (left) and hydrophobicity (right). Molecules are shown in two views 180° apart. Electrostatic potentials contoured from 10 kT (red) to +10 kT (blue) are plotted onto the molecular surface of MSP-1[19] from P. knowlesi, P. cynomolgi, and P. falciparum, respectively. Hydrophobicity values calculated from modified solvent transfer experiments (45) are contoured from 2 kcal/mol (most hydrophobic, in yellow) to 2 kcal/mol (hydrophilic, in green). The hydrophobic patches found on the surface tend to be from exposed portions of residues forming the interface between domains 1 and 2.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 7264-7269) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21303498 M.Mahdi Abdel Hamid, E.J.Remarque, I.M.El Hassan, A.A.Hussain, D.L.Narum, A.W.Thomas, C.H.Kocken, W.R.Weiss, and B.W.Faber (2011).
Malaria infection by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in Rhesus macaques.
  Malar J, 10, 29.  
19921275 S.Mazumdar, S.Sachdeva, V.S.Chauhan, and S.S.Yazdani (2010).
Identification of cultivation condition to produce correctly folded form of a malaria vaccine based on Plasmodium falciparum merozoite surface protein-1 in Escherichia coli.
  Bioprocess Biosyst Eng, 33, 719-730.  
19627632 A.A.Holder (2009).
The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria.
  Parasitology, 136, 1445-1456.  
18333885 P.R.Gilson, R.A.O'Donnell, T.Nebl, P.R.Sanders, M.E.Wickham, T.F.McElwain, Koning-Ward, and B.S.Crabb (2008).
MSP1(19) miniproteins can serve as targets for invasion inhibitory antibodies in Plasmodium falciparum provided they contain the correct domains for cell surface trafficking.
  Mol Microbiol, 68, 124-138.  
17173281 F.Autore, S.Melchiorre, J.Kleinjung, W.D.Morgan, and F.Fraternali (2007).
Interaction of malaria parasite-inhibitory antibodies with the merozoite surface protein MSP1(19) by computational docking.
  Proteins, 66, 513-527.  
16797221 G.A.Bentley (2006).
Functional and immunological insights from the three-dimensional structures of Plasmodium surface proteins.
  Curr Opin Microbiol, 9, 395-400.  
17068840 S.James, K.Moehle, A.Renard, M.S.Mueller, D.Vogel, R.Zurbriggen, G.Pluschke, and J.A.Robinson (2006).
Synthesis, solution structure and immune recognition of an epidermal growth factor-like domain from Plasmodium falciparum merozoite surface protein-1.
  Chembiochem, 7, 1943-1950.
PDB code: 2flg
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.