4k24

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'''Unreleased structure'''
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{{STRUCTURE_4k24| PDB=4k24 | SCENE= }}
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===Structure of anti-uPAR Fab ATN-658 in complex with uPAR===
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{{ABSTRACT_PUBMED_24465541}}
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The entry 4k24 is ON HOLD until Paper Publication
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==Disease==
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[[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>
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Authors: Huang, M.D., Xu, X., Yuan, C.
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==Function==
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[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. [[http://www.uniprot.org/uniprot/VTNC_HUMAN VTNC_HUMAN]] Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity. [[http://www.uniprot.org/uniprot/UPAR_HUMAN UPAR_HUMAN]] Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
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Description: Structure of anti-uPAR Fab ATN-658 in complex with uPAR
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==About this Structure==
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[[4k24]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K24 OCA].
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==Reference==
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<ref group="xtra">PMID:024465541</ref><references group="xtra"/><references/>
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[[Category: Mus musculus]]
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[[Category: U-plasminogen activator]]
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[[Category: Huang, M D.]]
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[[Category: Xu, X.]]
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[[Category: Yuan, C.]]
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[[Category: Immune system]]

Revision as of 18:01, 3 March 2014

Template:STRUCTURE 4k24

Contents

Structure of anti-uPAR Fab ATN-658 in complex with uPAR

Template:ABSTRACT PUBMED 24465541

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. [VTNC_HUMAN] Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity. [UPAR_HUMAN] Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.

About this Structure

4k24 is a 5 chain structure with sequence from [1] and Mus musculus. Full crystallographic information is available from OCA.

Reference

  • Xu X, Cai Y, Wei Y, Donate F, Juarez J, Parry G, Chen L, Meehan EJ, Ahn RW, Ugolkov A, Dubrovskyi O, O'Halloran TV, Huang M, Mazar AP. Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b (alphaM). PLoS One. 2014 Jan 21;9(1):e85349. doi: 10.1371/journal.pone.0085349. eCollection, 2014 Jan 21. PMID:24465541 doi:http://dx.doi.org/10.1371/journal.pone.0085349
  1. ↑ 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

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