1ppg

From Proteopedia

(Difference between revisions)

Revision as of 09:48, 27 November 2019

The refined 2.3 angstroms crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor

Structural highlights

1ppg is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
NonStd Res:	, ,
Activity:	Leukocyte elastase, with EC number 3.4.21.37
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

The stoichiometric complex formed between human leukocyte elastase and a synthetic MeO-Suc-Ala-Ala-Pro-Val chloromethyl ketone inhibitor was co-crystallized and its X-ray structure determined, using Patterson search methods. Its structure has been crystallographically refined to a final R value of 0.145 (8.0 and 2.3 A). The enzyme structure is very similar to that recently observed in a complex formed with the ovomucoid third domain from turkey [(1986) EMBO J. 5,2453-2458]. The rms deviation of all alpha-carbon atoms is 0.32 A. The peptidic inhibitor is bound in a similar overall conformation as the ovomucoid binding segment. Covalent bonds are formed between Val-P1 of the inhibitor and His-57 NE2 and Ser-195 OG of the enzyme. The carbonyl carbon is tetrahedrally deformed to a hemiketal. The valine side chain is arranged in the S1 pocket in the g-conformation.

The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor.,Wei AZ, Mayr I, Bode W FEBS Lett. 1988 Jul 18;234(2):367-73. PMID:3391280^[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
↑ Wei AZ, Mayr I, Bode W. The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor. FEBS Lett. 1988 Jul 18;234(2):367-73. PMID:3391280

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/1ppg"

@@ Line 1: / Line 1: @@
 ==The refined 2.3 angstroms crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor==
-<StructureSection load='1ppg' size='340' side='right' caption='[[1ppg]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='1ppg' size='340' side='right'caption='[[1ppg]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1ppg]] is a 2 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=1PPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PPG FirstGlance]. <br>
@@ Line 32: / Line 32: @@
 </div>
 <div class="pdbe-citations 1ppg" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Elastase 3D structures|Elastase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Leukocyte elastase]]
 [[Category: Bode, W]]

1ppg

From Proteopedia

Revision as of 09:48, 27 November 2019

The refined 2.3 angstroms crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor

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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