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5hgg

From Proteopedia

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Current revision

Crystal structure of uPA in complex with a camelid-derived antibody fragment

Structural highlights

5hgg is a 4 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.97Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

UROK_HUMAN Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:601709. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.^[1]

Function

UROK_HUMAN Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009, Dec 9. PMID:20007542 doi:10.1182/blood-2009-07-233965
↑ Kromann-Hansen T, Oldenburg E, Yung KW, Ghassabeh GH, Muyldermans S, Declerck PJ, Huang M, Andreasen PA, Ngo JC. A Camelid-derived Antibody Fragment Targeting the Active Site of a Serine Protease Balances between Inhibitor and Substrate Behavior. J Biol Chem. 2016 May 23. pii: jbc.M116.732503. PMID:27226628 doi:http://dx.doi.org/10.1074/jbc.M116.732503

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5hgg"

@@ Line 3: / Line 3: @@
 <StructureSection load='5hgg' size='340' side='right'caption='[[5hgg]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hgg]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Alpaca Alpaca] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HGG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5HGG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hgg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HGG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HGG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TWN:(3S)-3-[(2S,3S,4R)-3,4-DIMETHYLTETRAHYDROFURAN-2-YL]BUTYL+LAURATE'>TWN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.97&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLAU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TWN:(3S)-3-[(2S,3S,4R)-3,4-DIMETHYLTETRAHYDROFURAN-2-YL]BUTYL+LAURATE'>TWN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hgg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hgg OCA], [https://pdbe.org/5hgg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hgg RCSB], [https://www.ebi.ac.uk/pdbsum/5hgg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hgg ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hgg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hgg OCA], [http://pdbe.org/5hgg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hgg RCSB], [http://www.ebi.ac.uk/pdbsum/5hgg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hgg ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[http://omim.org/entry/601709 601709]]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
+[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://omim.org/entry/601709 601709]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
+[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 *[[Plasminogen activator|Plasminogen activator]]
 *[[Urokinase 3D Structures|Urokinase 3D Structures]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Alpaca]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: U-plasminogen activator]]
+[[Category: Vicugna pacos]]
-[[Category: Andreasen, P A]]
+[[Category: Andreasen PA]]
-[[Category: Kromann-Hansen, T]]
+[[Category: Kromann-Hansen T]]
-[[Category: Ngo, J C.K]]
+[[Category: Ngo JCK]]
-[[Category: Yung, K W.Y]]
+[[Category: Yung KWY]]
-[[Category: Hydrolase-inhibitor complex]]
-[[Category: Nanobody]]
-[[Category: Serine protease]]
-[[Category: Upa]]

5hgg

From Proteopedia

Current revision

Crystal structure of uPA in complex with a camelid-derived antibody fragment

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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