1b0f

From Proteopedia

(Difference between revisions)

Revision as of 05:34, 9 August 2023

CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146

Structural highlights

1b0f is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ELNE_HUMAN Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM: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.^[1] ^[2] Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM: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.^[3]

Function

ELNE_HUMAN Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.^[4]

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

A series of P2-modified, orally active peptidic inhibitors of human neutrophil elastase (HNE) are reported. These pentafluoroethyl ketone-based inhibitors were designed using pentafluoroethyl ketone 1 as a model. Rational structural modifications were made at the P3, P2, and activating group (AG) portions of 1 based on structure-activity relationships (SAR) developed from in vitro (measured Ki) data and information provided by modeling studies that docked inhibitor 1 into the active site of HNE. The modeling-based design was corroborated with X-ray crystallographic analysis of the complex between 1 and porcine pancreatic elastase (PPE) and subsequently the complex between 1 and HNE.

Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally active peptidyl pentafluoroethyl ketones.,Cregge RJ, Durham SL, Farr RA, Gallion SL, Hare CM, Hoffman RV, Janusz MJ, Kim HO, Koehl JR, Mehdi S, Metz WA, Peet NP, Pelton JT, Schreuder HA, Sunder S, Tardif C J Med Chem. 1998 Jul 2;41(14):2461-80. PMID:9651152^[5]

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

References

↑ Duan Z, Li FQ, Wechsler J, Meade-White K, Williams K, Benson KF, Horwitz M. A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia. Mol Cell Biol. 2004 Jan;24(1):58-70. PMID:14673143
↑ Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999 Dec;23(4):433-6. PMID:10581030 doi:10.1038/70544
↑ Germeshausen M, Zeidler C, Stuhrmann M, Lanciotti M, Ballmaier M, Welte K. Digenic mutations in severe congenital neutropenia. Haematologica. 2010 Jul;95(7):1207-10. doi: 10.3324/haematol.2009.017665. Epub, 2010 Mar 10. PMID:20220065 doi:10.3324/haematol.2009.017665
↑ Tralau T, Meyer-Hoffert U, Schroder JM, Wiedow O. Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis. Exp Dermatol. 2004 May;13(5):316-25. PMID:15140022 doi:10.1111/j.0906-6705.2004.00145.x
↑ Cregge RJ, Durham SL, Farr RA, Gallion SL, Hare CM, Hoffman RV, Janusz MJ, Kim HO, Koehl JR, Mehdi S, Metz WA, Peet NP, Pelton JT, Schreuder HA, Sunder S, Tardif C. Inhibition of human neutrophil elastase. 4. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of P2-modified, orally active peptidyl pentafluoroethyl ketones. J Med Chem. 1998 Jul 2;41(14):2461-80. PMID:9651152 doi:10.1021/jm970812e

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1b0f"

@@ Line 3: / Line 3: @@
 <StructureSection load='1b0f' size='340' side='right'caption='[[1b0f]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1b0f]] is a 1 chain structure 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=1B0F OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1B0F FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1b0f]] is a 1 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=1B0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B0F FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEI:1-{3-METHYL-2-[4-(MORPHOLINE-4-CARBONYL)-BENZOYLAMINO]-BUTYRYL}-PYRROLIDINE-2-CARBOXYLIC+ACID+(3,3,4,4,4-PENTAFLUORO-1-ISOPROPYL-2-OXO-BUTYL)-AMIDE'>SEI</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SEI:1-{3-METHYL-2-[4-(MORPHOLINE-4-CARBONYL)-BENZOYLAMINO]-BUTYRYL}-PYRROLIDINE-2-CARBOXYLIC+ACID+(3,3,4,4,4-PENTAFLUORO-1-ISOPROPYL-2-OXO-BUTYL)-AMIDE'>SEI</scene></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=1b0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b0f OCA], [http://pdbe.org/1b0f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1b0f RCSB], [http://www.ebi.ac.uk/pdbsum/1b0f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1b0f ProSAT]</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=1b0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b0f OCA], [https://pdbe.org/1b0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b0f RCSB], [https://www.ebi.ac.uk/pdbsum/1b0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b0f ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[http://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:[http://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>
+[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>
 == Function ==
-[[http://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>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 40: / Line 40: @@
 [[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Leukocyte elastase]]
+[[Category: Metz WA]]
-[[Category: Metz, W A]]
+[[Category: Peet NP]]
-[[Category: Peet, N P]]
+[[Category: Pelton JT]]
-[[Category: Pelton, J T]]
+[[Category: Schreuder HA]]
-[[Category: Schreuder, H A]]
+[[Category: Tardif C]]
-[[Category: Tardif, C]]
-[[Category: Fluoroethyl ketone]]
-[[Category: Hydrolase]]
-[[Category: Serine protease]]

1b0f

From Proteopedia

Revision as of 05:34, 9 August 2023

CRYSTAL STRUCTURE OF HUMAN NEUTROPHIL ELASTASE WITH MDL 101, 146

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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