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PDBsum entry 4x2t
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Hydrolase/hydrolase inhibitor
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PDB id
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4x2t
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PDB id:
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| Name: |
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Hydrolase/hydrolase inhibitor
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Title:
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X-ray crystal structure of the orally available aminopeptidase inhibitor, tosedostat, bound to the m17 leucyl aminopeptidase from p. Falciparum
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Structure:
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M17 leucyl aminopeptidase. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Fragment: unp residues 85 to 603. Engineered: yes. Mutation: yes
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Source:
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Plasmodium falciparum (isolate 3d7). Organism_taxid: 36329. Strain: isolate 3d7. Gene: lap, pf14_0439. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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2.73Å
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R-factor:
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0.223
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R-free:
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0.274
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Authors:
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N.Drinkwater,S.Mcgowan
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Key ref:
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N.Drinkwater
et al.
(2015).
X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.
Proteins,
83,
789-795.
PubMed id:
DOI:
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Date:
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27-Nov-14
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Release date:
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18-Feb-15
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PROCHECK
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Headers
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References
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Q8IL11
(Q8IL11_PLAF7) -
Leucine aminopeptidase from Plasmodium falciparum (isolate 3D7)
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Seq:
Struc:
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605 a.a.
516 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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Enzyme class 2:
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E.C.3.4.11.1
- leucyl aminopeptidase.
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Reaction:
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Release of an N-terminal amino acid, Xaa-|-Xbb-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Xbb may be Pro.
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Cofactor:
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Zn(2+)
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Enzyme class 3:
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E.C.3.4.13.-
- ?????
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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DOI no:
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Proteins
83:789-795
(2015)
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PubMed id:
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X-ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti-malarial drug targets PfA-M1 and PfA-M17.
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N.Drinkwater,
R.S.Bamert,
K.K.Sivaraman,
A.Paiardini,
S.McGowan.
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ABSTRACT
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New anti-malarial treatments are desperately required to face the spread of drug
resistant parasites. Inhibition of metalloaminopeptidases, PfA-M1 and PfA-M17,
is a validated therapeutic strategy for treatment of Plasmodium falciparum
malaria. Here, we describe the crystal structures of PfA-M1 and PfA-M17 bound to
chemotherapeutic agent Tosedostat. The inhibitor occupies the enzymes' putative
product egress channels in addition to the substrate binding pockets; however,
adopts different binding poses when bound to PfA-M1 and PfA-M17. These findings
will be valuable for the continued development of selective inhibitors of PfA-M1
and PfA-M17. Proteins 2015; 83:789-795. © 2015 Wiley Periodicals, Inc.
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Links
