5cuh

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==Crystal structure MMP-9 complexes with a constrained hydroxamate based inhibitor LT4==
==Crystal structure MMP-9 complexes with a constrained hydroxamate based inhibitor LT4==
<StructureSection load='5cuh' size='340' side='right' caption='[[5cuh]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
<StructureSection load='5cuh' size='340' side='right' caption='[[5cuh]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref>
[[http://www.uniprot.org/uniprot/MMP9_HUMAN MMP9_HUMAN]] May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.<ref>PMID:1480034</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Hodgkin's lymphoma (HL) is the most common malignant lymphoma in young adults in the western world. This disease is characterized by an overexpression of ADAM-10 with increased release of NKG2D ligands, involved in an impaired immune response against tumor cells. We designed and synthesized two new ADAM-10 selective inhibitors, 2 and 3 based on previously published ADAM-17 selective inhibitor 1. The most promising compound was the thiazolidine derivative 3, with nanomolar activity for ADAM-10, high selectivity over ADAM-17 and MMPs and good efficacy in reducing the shedding of NKG2D ligands (MIC-B and ULBP3) in three different HL cell lines at non-toxic doses. Molecular modeling studies were used to drive the design and X-ray crystallography studies were carried out to explain the selectivity of 3 for ADAM-10 over MMPs.
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Discovery of a new selective inhibitor of A Disintegrin And Metalloprotease 10 (ADAM-10) able to reduce the shedding of NKG2D ligands in Hodgkin's lymphoma cell models.,Camodeca C, Nuti E, Tepshi L, Boero S, Tuccinardi T, Stura EA, Poggi A, Zocchi MR, Rossello A Eur J Med Chem. 2016 Mar 23;111:193-201. doi: 10.1016/j.ejmech.2016.01.053. Epub , 2016 Jan 29. PMID:26871660<ref>PMID:26871660</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 5cuh" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Revision as of 15:53, 10 May 2016

Crystal structure MMP-9 complexes with a constrained hydroxamate based inhibitor LT4

5cuh, resolution 1.83Å

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