DB code: D00216

RLCP classification 1.13.30000.10 : Hydrolysis
CATH domain 2.40.10.10 : Thrombin, subunit H Catalytic domain
2.40.10.10 : Thrombin, subunit H Catalytic domain
E.C. 3.4.21.37
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.40.10.10 : Thrombin, subunit H M00139 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq MEROPS Pfam
P08246 Leukocyte elastase
EC 3.4.21.37
Elastase-2
Neutrophil elastase
PMN elastase
Bone marrow serine protease
Medullasin
Human leukocyte elastase
HLE
NP_001963.1 (Protein)
NM_001972.2 (DNA/RNA sequence)
S01.131 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
leukocyte elastase
lysosomal elastase
neutrophil elastase
polymorphonuclear leukocyte elastase
elastase
elaszym
serine elastase
lysosomal elastase
granulocyte elastase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P08246 ELNE_HUMAN Hydrolysis of proteins, including elastin. Preferential cleavage: Val-|-Xaa > Ala-|-Xaa. Interacts with NOTCH2NL.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00001 C00012 C00017 C00373 C00012 C00017 C00098 I00087 I00085 I00086
E.C.
Compound H2O Peptide Protein Elastin Peptide Protein Oligopeptide Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type H2O peptide/protein peptide/protein peptide/protein peptide/protein peptide/protein amine group,carboxyl group,peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
 		439221
 439221
1b0fA01 Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:SEI Unbound Unbound
1hneE01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:MSU-ALA-ALA-PRO-ALM (chain I)
1ppfE01 Unbound Analogue:LEU_18-GLU_19 (chain I) Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ppgE01 Unbound Unbound Unbound Analogue:HMB-ALA-ALA-PRO-VAF (chain I) Unbound Unbound Unbound Unbound Unbound
1h1bA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:151 Unbound
1h1bB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:151 Unbound
1b0fA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hneE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ppfE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ppgE02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1h1bA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1h1bB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P08246

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b0fA01 SER 195 GLY 193;SER 195
1hneE01 SER 195 GLY 193;SER 195
1ppfE01 SER 195 GLY 193;SER 195
1ppgE01 SER 195 GLY 193;SER 195
1h1bA01 SER 195 GLY 193;SER 195
1h1bB01 SER 195 GLY 193;SER 195
1b0fA02 HIS 57;ASP 102
1hneE02 HIS 57;ASP 102
1ppfE02 HIS 57;ASP 102
1ppgE02 HIS 57;ASP 102
1h1bA02 HIS 57;ASP 102
1h1bB02 HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
p.372
[4]
p.9
[14]
p.2468

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
Medline ID 87053808
PubMed ID 3640709
Journal EMBO J
Year 1986
Volume 5
Pages 2453-8
Authors Bode W, Wei AZ, Huber R, Meyer E, Travis J, Neumann S
Title X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor.
Related PDB 1ppf
Related UniProtKB P08246
[2]
Resource
Comments
Medline ID
PubMed ID 3415672
Journal Biochem J
Year 1988
Volume 252
Pages 515-9
Authors Redini F, Tixier JM, Petitou M, Choay J, Robert L, Hornebeck W
Title Inhibition of leucocyte elastase by heparin and its derivatives.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 88271660
PubMed ID 3391280
Journal FEBS Lett
Year 1988
Volume 234
Pages 367-73
Authors Wei AZ, Mayr I, Bode W
Title The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor.
Related PDB 1ppg
Related UniProtKB P08246
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS).
Medline ID 89098932
PubMed ID 2911584
Journal Proc Natl Acad Sci U S A
Year 1989
Volume 86
Pages 7-11
Authors Navia MA, McKeever BM, Springer JP, Lin TY, Williams HR, Fluder EM, Dorn CP, Hoogsteen K
Title Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution.
Related PDB 1hne
Related UniProtKB P08246
[5]
Resource
Comments
Medline ID
PubMed ID 7986820
Journal Biochim Biophys Acta
Year 1994
Volume 1227
Pages 130-6
Authors Groutas WC, Huang H, Epp JB, Venkataraman R, McClenahan JJ, Tagusagawa F
Title Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8075302
Journal Drug Des Discov
Year 1994
Volume 11
Pages 149-57
Authors Groutas WC, Brubaker MJ, Chong LS, Epp JB, Huang H, Keller CE, McClenahan JJ, Givens RS, Singh R, Zandler ME, et al
Title Derivatives of 3-alkyl-N-hydroxysuccinimide: probing the effect of structure on bioactivity toward human leukocyte elastase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7830264
Journal J Med Chem
Year 1995
Volume 38
Pages 223-33
Authors Burkhart JP, Koehl JR, Mehdi S, Durham SL, Janusz MJ, Huber EW, Angelastro MR, Sunder S, Metz WA, Shum PW, et al
Title Inhibition of human neutrophil elastase. 3. An orally active enol acetate prodrug.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 7479933
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 11044-8
Authors Lin Y, Padmapriya A, Morden KM, Jayasena SD
Title Peptide conjugation to an in vitro-selected DNA ligand improves enzyme inhibition.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8703486
Journal Am J Respir Cell Mol Biol
Year 1996
Volume 15
Pages 283-91
Authors Ying QL, Kemme M, Simon SR
Title Alginate, the slime exopolysaccharide of Pseudomonas aeruginosa, binds human leukocyte elastase, retards inhibition by alpha 1-proteinase inhibitor, and accelerates inhibition by secretory leukoprotease inhibitor.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8894097
Journal Bioorg Med Chem
Year 1996
Volume 4
Pages 1393-400
Authors Groutas WC, Epp JB, Venkataraman R, Kuang R, Truong TM, McClenahan JJ, Prakash O
Title Design, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8901643
Journal J Mol Graph
Year 1996
Volume 14
Pages 158-67, 145
Authors Vergely I, Laugaa P, Reboud-Ravaux M
Title Interaction of human leukocyte elastase with a N-aryl azetidinone suicide substrate: Conformational analyses based on the mechanism of action of serine proteinases.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9398290
Journal Biochemistry
Year 1997
Volume 36
Pages 15624-31
Authors Mely Y, Cadene M, Sylte I, Bieth JG
Title Mapping the suramin-binding sites of human neutrophil elastase: investigation by fluorescence resonance energy transfer and molecular modeling.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9864442
Journal Biochemistry (Mosc)
Year 1998
Volume 63
Pages 1119-21
Authors Malykh EV, Tyurina OP, Balabushevitch NG, Larionova NI
Title Effect of hydrophobization of basic pancreatic proteinase inhibitor on the inhibition of bovine trypsin and human leukocyte elastase.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9651152
Journal J Med Chem
Year 1998
Volume 41
Pages 2461-80
Authors 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
Title 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.
Related PDB 1b0f
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 10082946
Journal Biochim Biophys Acta
Year 1999
Volume 1430
Pages 179-90
Authors Morrison HM, Welgus HG, Owen CA, Stockley RA, Campbell EJ
Title Interaction between leukocyte elastase and elastin: quantitative and catalytic analyses.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10476876
Journal Bioorg Med Chem Lett
Year 1999
Volume 9
Pages 2397-402
Authors Nakanishi I, Kinoshita T, Tada T, Fujita T, Hatanaka H, Sato A
Title Molecular structure of FR901277, a novel inhibitor of human leukocyte elastase, and its binding mode simulation.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 10639285
Journal J Med Chem
Year 1999
Volume 42
Pages 5437-47
Authors G]utschow M, Kuerschner L, Neumann U, Pietsch M, L]oser R, Koglin N, Eger K
Title 2-(diethylamino)thieno inverted question mark1,3oxazin-4-ones as stable inhibitors of human leukocyte elastase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10581030
Journal Nat Genet
Year 1999
Volume 23
Pages 433-6
Authors Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC
Title Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 10896125
Journal Bioorg Med Chem
Year 2000
Volume 8
Pages 1489-501
Authors Pochet L, Doucet C, Dive G, Wouters J, Masereel B, Reboud-Ravaux M, Pirotte B
Title Coumarinic derivatives as mechanism-based inhibitors of alpha-chymotrypsin and human leukocyte elastase.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10850955
Journal J Enzyme Inhib
Year 2000
Volume 15
Pages 63-77
Authors Li-Pan ZS, Joshi HV, Digenis GA
Title Synthesis and mechanism of action of novel thiocarbamate inhibitors of human leukocyte elastase.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11150162
Journal J Med Chem
Year 2000
Volume 43
Pages 4927-9
Authors Ohmoto 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
Title Design and synthesis of new orally active nonpeptidic inhibitors of human neutrophil elastase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11101139
Journal Mol Cells
Year 2000
Volume 10
Pages 498-504
Authors Kim WM, Kang K
Title Enzymatic and molecular biochemical characterizations of human neutrophil elastases and a cathepsin G-like enzyme.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11206469
Journal Bioorg Med Chem Lett
Year 2001
Volume 11
Pages 243-6
Authors Macdonald 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
Title Intracellular inhibition of human neutrophil elastase by orally active pyrrolidine-trans-lactams.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11278653
Journal J Biol Chem
Year 2001
Volume 276
Pages 14230-41
Authors Li FQ, Horwitz M
Title Characterization of mutant neutrophil elastase in severe congenital neutropenia.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12190311
Journal J Med Chem
Year 2002
Volume 45
Pages 3878-90
Authors Macdonald 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
Title Discovery 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 PDB 1h1b
Related UniProtKB

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.

Created Updated
2004-08-26 2011-02-18