EzCatDB: D00216
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DB codeD00216
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 12.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 22.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.37

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00227,M00209,D00194,D00197,D00211,D00212,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411

Enzyme Name
UniProtKBKEGG

P08246
Protein nameLeukocyte elastaseleukocyte elastase
lysosomal elastase
neutrophil elastase
polymorphonuclear leukocyte elastase
elastase
elaszym
serine elastase
lysosomal elastase
granulocyte elastase
SynonymsEC 3.4.21.37
Elastase-2
Neutrophil elastase
PMN elastase
Bone marrow serine protease
Medullasin
Human leukocyte elastase
HLE
RefSeqNP_001963.1 (Protein)
NM_001972.2 (DNA/RNA sequence)
MEROPSS01.131 (Serine)
PfamPF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP08246
Entry nameELNE_HUMAN
ActivityHydrolysis of proteins, including elastin. Preferential cleavage: Val-|-Xaa > Ala-|-Xaa.
SubunitInteracts with NOTCH2NL.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00001C00012C00017C00373C00012C00017C00098I00087I00085I00086
CompoundH2OPeptideProteinElastinPeptideProteinOligopeptidePeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
TypeH2Opeptide/proteinpeptide/proteinpeptide/proteinpeptide/proteinpeptide/proteinamine group,carboxyl group,peptide/protein


ChEBI15377









PubChem962
22247451


439221






                  
1b0fA01 UnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:SEIUnboundUnbound
1hneE01 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:MSU-ALA-ALA-PRO-ALM(chain I)
1ppfE01 UnboundAnalogue:LEU 18-GLU 19(chain I)UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ppgE01 UnboundUnboundUnboundAnalogue:HMB-ALA-ALA-PRO-VAF(chain I)UnboundUnboundUnboundUnboundUnbound
1h1bA01 UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:151Unbound
1h1bB01 UnboundUnboundUnboundUnboundUnboundUnboundUnboundIntermediate-analogue:151Unbound
1b0fA02 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1hneE02 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ppfE02 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ppgE02 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1h1bA02 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1h1bB02 UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P08246
pdbCatalytic residuesMain-chain involved in catalysis
          
1b0fA01SER 195
GLY 193;SER 195
1hneE01SER 195
GLY 193;SER 195
1ppfE01SER 195
GLY 193;SER 195
1ppgE01SER 195
GLY 193;SER 195
1h1bA01SER 195
GLY 193;SER 195
1h1bB01SER 195
GLY 193;SER 195
1b0fA02HIS 57;ASP 102
 
1hneE02HIS 57;ASP 102
 
1ppfE02HIS 57;ASP 102
 
1ppgE02HIS 57;ASP 102
 
1h1bA02HIS 57;ASP 102
 
1h1bB02HIS 57;ASP 102
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.372
[4]p.9
[14]p.2468

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
Medline ID87053808
PubMed ID3640709
JournalEMBO J
Year1986
Volume5
Pages2453-8
AuthorsBode W, Wei AZ, Huber R, Meyer E, Travis J, Neumann S
TitleX-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor.
Related PDB1ppf
Related UniProtKBP08246
[2]
PubMed ID3415672
JournalBiochem J
Year1988
Volume252
Pages515-9
AuthorsRedini F, Tixier JM, Petitou M, Choay J, Robert L, Hornebeck W
TitleInhibition of leucocyte elastase by heparin and its derivatives.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID88271660
PubMed ID3391280
JournalFEBS Lett
Year1988
Volume234
Pages367-73
AuthorsWei AZ, Mayr I, Bode W
TitleThe refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor.
Related PDB1ppg
Related UniProtKBP08246
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS).
Medline ID89098932
PubMed ID2911584
JournalProc Natl Acad Sci U S A
Year1989
Volume86
Pages7-11
AuthorsNavia MA, McKeever BM, Springer JP, Lin TY, Williams HR, Fluder EM, Dorn CP, Hoogsteen K
TitleStructure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution.
Related PDB1hne
Related UniProtKBP08246
[5]
PubMed ID7986820
JournalBiochim Biophys Acta
Year1994
Volume1227
Pages130-6
AuthorsGroutas WC, Huang H, Epp JB, Venkataraman R, McClenahan JJ, Tagusagawa F
TitleMechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils.
[6]
PubMed ID8075302
JournalDrug Des Discov
Year1994
Volume11
Pages149-57
AuthorsGroutas WC, Brubaker MJ, Chong LS, Epp JB, Huang H, Keller CE, McClenahan JJ, Givens RS, Singh R, Zandler ME, et al
TitleDerivatives of 3-alkyl-N-hydroxysuccinimide: probing the effect of structure on bioactivity toward human leukocyte elastase.
[7]
PubMed ID7830264
JournalJ Med Chem
Year1995
Volume38
Pages223-33
AuthorsBurkhart JP, Koehl JR, Mehdi S, Durham SL, Janusz MJ, Huber EW, Angelastro MR, Sunder S, Metz WA, Shum PW, et al
TitleInhibition of human neutrophil elastase. 3. An orally active enol acetate prodrug.
[8]
PubMed ID7479933
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages11044-8
AuthorsLin Y, Padmapriya A, Morden KM, Jayasena SD
TitlePeptide conjugation to an in vitro-selected DNA ligand improves enzyme inhibition.
[9]
PubMed ID8703486
JournalAm J Respir Cell Mol Biol
Year1996
Volume15
Pages283-91
AuthorsYing QL, Kemme M, Simon SR
TitleAlginate, the slime exopolysaccharide of Pseudomonas aeruginosa, binds human leukocyte elastase, retards inhibition by alpha 1-proteinase inhibitor, and accelerates inhibition by secretory leukoprotease inhibitor.
[10]
PubMed ID8894097
JournalBioorg Med Chem
Year1996
Volume4
Pages1393-400
AuthorsGroutas WC, Epp JB, Venkataraman R, Kuang R, Truong TM, McClenahan JJ, Prakash O
TitleDesign, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.
[11]
PubMed ID8901643
JournalJ Mol Graph
Year1996
Volume14
Pages158-67, 145
AuthorsVergely I, Laugaa P, Reboud-Ravaux M
TitleInteraction of human leukocyte elastase with a N-aryl azetidinone suicide substrate: Conformational analyses based on the mechanism of action of serine proteinases.
[12]
PubMed ID9398290
JournalBiochemistry
Year1997
Volume36
Pages15624-31
AuthorsMely Y, Cadene M, Sylte I, Bieth JG
TitleMapping the suramin-binding sites of human neutrophil elastase: investigation by fluorescence resonance energy transfer and molecular modeling.
[13]
PubMed ID9864442
JournalBiochemistry (Mosc)
Year1998
Volume63
Pages1119-21
AuthorsMalykh EV, Tyurina OP, Balabushevitch NG, Larionova NI
TitleEffect of hydrophobization of basic pancreatic proteinase inhibitor on the inhibition of bovine trypsin and human leukocyte elastase.
[14]
CommentsX-ray crystallography
PubMed ID9651152
JournalJ Med Chem
Year1998
Volume41
Pages2461-80
AuthorsCregge 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
TitleInhibition 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.
Related PDB1b0f
[15]
PubMed ID10082946
JournalBiochim Biophys Acta
Year1999
Volume1430
Pages179-90
AuthorsMorrison HM, Welgus HG, Owen CA, Stockley RA, Campbell EJ
TitleInteraction between leukocyte elastase and elastin: quantitative and catalytic analyses.
[16]
PubMed ID10476876
JournalBioorg Med Chem Lett
Year1999
Volume9
Pages2397-402
AuthorsNakanishi I, Kinoshita T, Tada T, Fujita T, Hatanaka H, Sato A
TitleMolecular structure of FR901277, a novel inhibitor of human leukocyte elastase, and its binding mode simulation.
[17]
PubMed ID10639285
JournalJ Med Chem
Year1999
Volume42
Pages5437-47
AuthorsG]utschow M, Kuerschner L, Neumann U, Pietsch M, L]oser R, Koglin N, Eger K
Title2-(diethylamino)thieno inverted question mark1,3oxazin-4-ones as stable inhibitors of human leukocyte elastase.
[18]
PubMed ID10581030
JournalNat Genet
Year1999
Volume23
Pages433-6
AuthorsHorwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC
TitleMutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis.
[19]
PubMed ID10896125
JournalBioorg Med Chem
Year2000
Volume8
Pages1489-501
AuthorsPochet L, Doucet C, Dive G, Wouters J, Masereel B, Reboud-Ravaux M, Pirotte B
TitleCoumarinic derivatives as mechanism-based inhibitors of alpha-chymotrypsin and human leukocyte elastase.
[20]
PubMed ID10850955
JournalJ Enzyme Inhib
Year2000
Volume15
Pages63-77
AuthorsLi-Pan ZS, Joshi HV, Digenis GA
TitleSynthesis and mechanism of action of novel thiocarbamate inhibitors of human leukocyte elastase.
[21]
PubMed ID11150162
JournalJ Med Chem
Year2000
Volume43
Pages4927-9
AuthorsOhmoto K, Yamamoto T, Horiuchi T, Imanishi H, Odagaki Y, Kawabata K, Sekioka T, Hirota Y, Matsuoka S, Nakai H, Toda M, Cheronis JC, Spruce LW, Gyorkos A, Wieczorek M
TitleDesign and synthesis of new orally active nonpeptidic inhibitors of human neutrophil elastase.
[22]
PubMed ID11101139
JournalMol Cells
Year2000
Volume10
Pages498-504
AuthorsKim WM, Kang K
TitleEnzymatic and molecular biochemical characterizations of human neutrophil elastases and a cathepsin G-like enzyme.
[23]
PubMed ID11206469
JournalBioorg Med Chem Lett
Year2001
Volume11
Pages243-6
AuthorsMacdonald SJ, Dowle MD, Harrison LA, Spooner JE, Shah P, Johnson MR, Inglis GG, Clarke GD, Belton DJ, Smith RA, Molloy CR, Dixon M, Murkitt G, Godward RE, Skarzynski T, Singh OM, Kumar KA, Hodgson ST, McDonald E, Hardy GW, Finch H, Humphreys DC, Fleetwood G
TitleIntracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams.
[24]
PubMed ID11278653
JournalJ Biol Chem
Year2001
Volume276
Pages14230-41
AuthorsLi FQ, Horwitz M
TitleCharacterization of mutant neutrophil elastase in severe congenital neutropenia.
[25]
PubMed ID12190311
JournalJ Med Chem
Year2002
Volume45
Pages3878-90
AuthorsMacdonald SJ, Dowle MD, Harrison LA, Clarke GD, Inglis GG, Johnson MR, Shah P, Smith RA, Amour A, Fleetwood G, Humphreys DC, Molloy CR, Dixon M, Godward RE, Wonacott AJ, Singh OM, Hodgson ST, Hardy GW
TitleDiscovery of further pyrrolidine trans-lactams as inhibitors of human neutrophil elastase (HNE) with potential as development candidates and the crystal structure of HNE complexed with an inhibitor (GW475151).
Related PDB1h1b

comments
This enzyme belongs to the peptidase family S1.
This enzyme has got a catalytic triad composed of His57, Asp102 and Ser195, which is a signature of serine proteases. Ser195 acts as the nucleophile to form a covalent-bonded intermediate.

createdupdated
2004-08-262011-02-18


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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