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5hdo

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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hdo OCA], [http://pdbe.org/5hdo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hdo RCSB], [http://www.ebi.ac.uk/pdbsum/5hdo PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hdo OCA], [http://pdbe.org/5hdo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hdo RCSB], [http://www.ebi.ac.uk/pdbsum/5hdo PDBsum]</span></td></tr>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A peptide segment that binds the active site of a serine protease in a substrate-like manner may behave like an inhibitor or a substrate. However, there is sparse information on which factors determine which behavior a particular peptide segment will exhibit. Here, we describe the first X-ray crystal structure of a nanobody in complex with a serine protease. The nanobody displays a new type of interaction between an antibody and a serine protease as it inserts its CDR-H3 loop into the active site of the protease in a substrate-like manner. The unique binding mechanism causes the nanobody to behave as a strong inhibitor as well as a poor substrate. Intriguingly, its substrate behavior is incomplete, as 30-40% of the nanobody remained intact and inhibitory after prolonged incubation with uPA. Biochemical analysis reveals that an intra-loop interaction network within the CDR-H3 of the nanobody balances its inhibitor versus substrate behavior. Collectively, our results unveil molecular factors, which may be a general mechanism to determine the substrate versus inhibitor behavior of other protease inhibitors.
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A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior.,Kromann-Hansen T, Oldenburg E, Yung KW, Ghassabeh GH, Muyldermans S, Declerck PJ, Huang M, Andreasen PA, Ngo JC J Biol Chem. 2016 May 23. pii: jbc.M116.732503. PMID:27226628<ref>PMID:27226628</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5hdo" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Kromann-Hansen, T]]
[[Category: Kromann-Hansen, T]]
[[Category: Immune system]]
[[Category: Immune system]]

Revision as of 07:42, 20 June 2016

Crystal structure of a nanobody raised against urokinase-type plasminogen activator

5hdo, resolution 2.16Å

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