1op9

From Proteopedia

(Difference between revisions)

Revision as of 07:39, 15 February 2018

Complex of human lysozyme with camelid VHH HL6 antibody fragment

Structural highlights

1op9 is a 2 chain structure with sequence from Arabian camel and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	LYZ OR LZM (HUMAN)
Activity:	Lysozyme, with EC number 3.2.1.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[LYSC_HUMAN] Defects in LYZ are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.^[1]

Function

[LYSC_HUMAN] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Amyloid diseases are characterized by an aberrant assembly of a specific protein or protein fragment into fibrils and plaques that are deposited in various organs and tissues, often with serious pathological consequences. Non-neuropathic systemic amyloidosis is associated with single point mutations in the gene coding for human lysozyme. Here we report that a single-domain fragment of a camelid antibody raised against wild-type human lysozyme inhibits the in vitro aggregation of its amyloidogenic variant, D67H. Our structural studies reveal that the epitope includes neither the site of mutation nor most residues in the region of the protein structure that is destabilized by the mutation. Instead, the binding of the antibody fragment achieves its effect by restoring the structural cooperativity characteristic of the wild-type protein. This appears to occur at least in part through the transmission of long-range conformational effects to the interface between the two structural domains of the protein. Thus, reducing the ability of an amyloidogenic protein to form partly unfolded species can be an effective method of preventing its aggregation, suggesting approaches to the rational design of therapeutic agents directed against protein deposition diseases.

A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme.,Dumoulin M, Last AM, Desmyter A, Decanniere K, Canet D, Larsson G, Spencer A, Archer DB, Sasse J, Muyldermans S, Wyns L, Redfield C, Matagne A, Robinson CV, Dobson CM Nature. 2003 Aug 14;424(6950):783-8. PMID:12917687^[2]

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

References

↑ Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ, et al.. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. 1993 Apr 8;362(6420):553-7. PMID:8464497 doi:http://dx.doi.org/10.1038/362553a0
↑ Dumoulin M, Last AM, Desmyter A, Decanniere K, Canet D, Larsson G, Spencer A, Archer DB, Sasse J, Muyldermans S, Wyns L, Redfield C, Matagne A, Robinson CV, Dobson CM. A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme. Nature. 2003 Aug 14;424(6950):783-8. PMID:12917687 doi:http://dx.doi.org/10.1038/nature01870

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1op9"

@@ Line 1: / Line 1: @@
 ==Complex of human lysozyme with camelid VHH HL6 antibody fragment==
 <StructureSection load='1op9' size='340' side='right' caption='[[1op9]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LYZ OR LZM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </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=1op9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1op9 OCA], [http://pdbe.org/1op9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1op9 RCSB], [http://www.ebi.ac.uk/pdbsum/1op9 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=1op9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1op9 OCA], [http://pdbe.org/1op9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1op9 RCSB], [http://www.ebi.ac.uk/pdbsum/1op9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1op9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/op/1op9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/op/1op9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1op9 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 1op9" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Lysozyme 3D structures|Lysozyme 3D structures]]
 == References ==
 <references/>

1op9

From Proteopedia

Revision as of 07:39, 15 February 2018

Complex of human lysozyme with camelid VHH HL6 antibody fragment

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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