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PDBsum entry 4tpv
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Blood clotting
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PDB id
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4tpv
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References listed in PDB file
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Key reference
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Title
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The structure of hookworm platelet inhibitor (hpi), A cap superfamily member from ancylostoma caninum.
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Authors
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D.Ma,
I.M.Francischetti,
J.M.Ribeiro,
J.F.Andersen.
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Ref.
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Acta Crystallogr F Struct Biol Commun, 2015,
71,
643-649.
[DOI no: ]
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PubMed id
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Abstract
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Secreted protein components of hookworm species include a number of
representatives of the cysteine-rich/antigen 5/pathogenesis-related 1 (CAP)
protein family known as Ancylostoma-secreted proteins (ASPs). Some of these have
been considered as candidate antigens for the development of vaccines against
hookworms. The functions of most CAP superfamily members are poorly understood,
but one form, the hookworm platelet inhibitor (HPI), has been isolated as a
putative antagonist of the platelet integrins αIIbβ3 and α2β1. Here, the
crystal structure of HPI is described and its structural features are examined
in relation to its possible function. The HPI structure is similar to those of
other ASPs and shows incomplete conservation of the sequence motifs CAP1 and
CAP2 that are considered to be diagnostic of CAP superfamily members. The
asymmetric unit of the HPI crystal contains a dimer with an extensive
interaction interface, but chromatographic measurements indicate that it is
primarily monomeric in solution. In the dimeric structure, the putative
active-site cleft areas from both monomers are united into a single negatively
charged depression. A potential Lys-Gly-Asp disintegrin-like motif was
identified in the sequence of HPI, but is not positioned at the apex of a tight
turn, making it unlikely that it interacts with the integrin. Recombinant HPI
produced in Escherichia coli was found not to inhibit the adhesion of human
platelets to collagen or fibrinogen, despite having a native structure as shown
by X-ray diffraction. This result corroborates previous analyses of recombinant
HPI and suggests that it might require post-translational modification or have a
different biological function.
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