1hne

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[[Image:1hne.png|left|200px]]
 
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==Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-angstroms resolution==
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The line below this paragraph, containing "STRUCTURE_1hne", creates the "Structure Box" on the page.
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<StructureSection load='1hne' size='340' side='right'caption='[[1hne]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1hne]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HNE FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ALV:(2S)-2-AMINOPROPANE-1,1-DIOL'>ALV</scene>, <scene name='pdbligand=MSU:SUCCINIC+ACID+MONOMETHYL+ESTER'>MSU</scene></td></tr>
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{{STRUCTURE_1hne| PDB=1hne | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hne OCA], [https://pdbe.org/1hne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hne RCSB], [https://www.ebi.ac.uk/pdbsum/1hne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hne ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[https://omim.org/entry/162800 162800]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.<ref>PMID:14673143</ref> <ref>PMID:10581030</ref> Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM:[https://omim.org/entry/202700 202700]. SCN1 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.<ref>PMID:20220065</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hn/1hne_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1hne ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinyl-Ala-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refined to an R factor of 16.4% at 1.84-A resolution. Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a beta-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highly asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.
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===STRUCTURE OF HUMAN NEUTROPHIL ELASTASE IN COMPLEX WITH A PEPTIDE CHLOROMETHYL KETONE INHIBITOR AT 1.84-ANGSTROMS RESOLUTION===
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Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution.,Navia MA, McKeever BM, Springer JP, Lin TY, Williams HR, Fluder EM, Dorn CP, Hoogsteen K Proc Natl Acad Sci U S A. 1989 Jan;86(1):7-11. PMID:2911584<ref>PMID:2911584</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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The line below this paragraph, {{ABSTRACT_PUBMED_2911584}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1hne" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 2911584 is the PubMed ID number.
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{{ABSTRACT_PUBMED_2911584}}
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==About this Structure==
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[[1hne]] is a 2 chain structure of [[Elastase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HNE OCA].
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==See Also==
==See Also==
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*[[Elastase]]
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*[[Elastase 3D structures|Elastase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:2911584</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Leukocyte elastase]]
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[[Category: Large Structures]]
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[[Category: Dorn, C P.]]
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[[Category: Dorn CP]]
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[[Category: Fluder, E M.]]
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[[Category: Fluder EM]]
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[[Category: Hoogsteen, K.]]
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[[Category: Hoogsteen K]]
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[[Category: Lin, T Y.]]
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[[Category: Lin T-Y]]
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[[Category: Mckeever, B M.]]
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[[Category: Mckeever BM]]
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[[Category: Navia, M A.]]
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[[Category: Navia MA]]
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[[Category: Springer, J P.]]
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[[Category: Springer JP]]
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[[Category: Williams, H R.]]
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[[Category: Williams HR]]

Current revision

Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-angstroms resolution

PDB ID 1hne

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