DB code: D00433

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. 3.4.21.76
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 D00434 D00435 M00227 M00209 D00194 D00197 D00211 D00212 D00216 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
P24158 Myeloblastin
EC 3.4.21.76
Leukocyte proteinase 3
PR-3
PR3
AGP7
Wegener autoantigen
P29
C-ANCA antigen
Neutrophil proteinase 4
NP-4
NP_002768.3 (Protein)
NM_002777.3 (DNA/RNA sequence)
S01.134 (Serine)
PF00089 (Trypsin)
[Graphical View]

KEGG enzyme name
myeloblastin
leukocyte proteinase 3
leukocyte proteinase 4
Wegener's granulomatosis autoantigen
proteinase PR-3
proteinase-3
PMNL proteinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P24158 PRTN3_HUMAN Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00012 C00017 C00001 C00012 C00017 I00087 I00085 I00086
E.C.
Compound Peptide Protein H2O Peptide Protein Peptidyl-tetrahedral intermediate Acyl-enzyme Tetrahedral intermediate
Type peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 15377
 15377
PubChem 22247451
 962
 22247451
 962
1fujA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujC02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1fujD02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P24158

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fujA01 SER 195 GLY 193;SER 195
1fujB01 SER 195 GLY 193;SER 195
1fujC01 SER 195 GLY 193;SER 195
1fujD01 SER 195 GLY 193;SER 195
1fujA02 HIS 57;ASP 102
1fujB02 HIS 57;ASP 102
1fujC02 HIS 57;ASP 102
1fujD02 HIS 57;ASP 102

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments IDENTITY OF WEGENER'S AUTOANTIGEN WITH PROTEINASE 3.
Medline ID 91055123
PubMed ID 2242436
Journal Blood
Year 1990
Volume 76
Pages 2162
Authors Gupta SK, Niles JL, McCluskey RT, Arnaout MA
Title Identity of Wegener's autoantigen (p29) with proteinase 3 and myeloblastin.
Related PDB
Related UniProtKB P24158
[2]
Resource
Comments
Medline ID
PubMed ID 2258701
Journal J Exp Med
Year 1990
Volume 172
Pages 1709-15
Authors Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE
Title Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1459241
Journal FEBS Lett
Year 1992
Volume 314
Pages 117-21
Authors Dolman KM, van de Wiel BA, Kam CM, Abbink JJ, Hack CE, Sonnenberg A, Powers JC, von dem Borne AE, Goldschmeding R
Title Determination of proteinase 3-alpha 1-antitrypsin complexes in inflammatory fluids.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1380042
Journal J Immunol
Year 1992
Volume 149
Pages 1409-15
Authors Bini P, Gabay JE, Teitel A, Melchior M, Zhou JL, Elkon KB
Title Antineutrophil cytoplasmic autoantibodies in Wegener's granulomatosis recognize conformational epitope(s) on proteinase 3.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7925979
Journal FEBS Lett
Year 1994
Volume 352
Pages 231-5
Authors Padrines M, Wolf M, Walz A, Baggiolini M
Title Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8157982
Journal J Immunol
Year 1994
Volume 152
Pages 4722-37
Authors Williams RC Jr, Staud R, Malone CC, Payabyab J, Byres L, Underwood D
Title Epitopes on proteinase-3 recognized by antibodies from patients with Wegener's granulomatosis.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8581420
Journal Bioorg Med Chem
Year 1995
Volume 3
Pages 375-81
Authors Groutas WC, Brubaker MJ, Chong LS, Venkataraman R, Huang H, Epp JB, Kuang R, Hoidal JR
Title Design, synthesis and biological evaluation of succinimide derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 7796053
Journal Bioorg Med Chem
Year 1995
Volume 3
Pages 187-93
Authors Groutas WC, Chong LS, Venkataraman R, Epp JB, Kuang R, Houser-Archield N, Hoidal JR
Title The Gabriel-Colman rearrangement in biological systems: design, synthesis and biological evaluation of phthalimide and saccharin derivatives as potential mechanism-based inhibitors of human leukocyte elastase, cathepsin G and proteinase 3.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7796046
Journal Bioorg Med Chem
Year 1995
Volume 3
Pages 125-8
Authors Groutas WC, Venkataraman R, Chong LS, Yoder JE, Epp JB, Stanga MA, Kim EH
Title Isoxazoline derivatives as potential inhibitors of the proteolytic enzymes human leukocyte elastase, cathepsin G and proteinase 3: a structure-activity relationship study.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8806743
Journal Arch Biochem Biophys
Year 1996
Volume 332
Pages 335-40
Authors Groutas WC, Chong LS, Venkataraman R, Kuang R, Epp JB, Houser-Archield N, Huang H, Hoidal JR
Title Amino acid-derived phthalimide and saccharin derivatives as inhibitors of human leukocyte elastase, cathepsin G, and proteinase 3.
Related PDB
Related UniProtKB
[11]
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
[12]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID 96346178
PubMed ID 8757293
Journal J Mol Biol
Year 1996
Volume 261
Pages 267-78
Authors Fujinaga M, Chernaia MM, Halenbeck R, Koths K, James MN
Title The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies.
Related PDB 1fuj
Related UniProtKB P24158
[13]
Resource
Comments
Medline ID
PubMed ID 9125494
Journal Biochemistry
Year 1997
Volume 36
Pages 4739-50
Authors Groutas WC, Kuang R, Venkataraman R, Epp JB, Ruan S, Prakash O
Title Structure-based design of a general class of mechanism-based inhibitors of the serine proteinases employing a novel amino acid-derived heterocyclic scaffold.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9058715
Journal Blood
Year 1997
Volume 89
Pages 1944-53
Authors Renesto P, Si-Tahar M, Moniatte M, Balloy V, Van Dorsselaer A, Pidard D, Chignard M
Title Specific inhibition of thrombin-induced cell activation by the neutrophil proteinases elastase, cathepsin G, and proteinase 3: evidence for distinct cleavage sites within the aminoterminal domain of the thrombin receptor.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9092534
Journal J Biol Chem
Year 1997
Volume 272
Pages 9950-5
Authors Cadene M, Duranton J, North A, Si-Tahar M, Chignard M, Bieth JG
Title Inhibition of neutrophil serine proteinases by suramin.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9681132
Journal Bioorg Med Chem
Year 1998
Volume 6
Pages 661-71
Authors Groutas WC, Kuang R, Ruan S, Epp JB, Venkataraman R, Truong TM
Title Potent and specific inhibition of human leukocyte elastase, cathepsin G and proteinase 3 by sulfone derivatives employing the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9756722
Journal Clin Immunol Immunopathol
Year 1998
Volume 89
Pages 35-43
Authors Davis JA, Peen E, Williams RC, Perkins S, Malone CC, McCormack WT, Csernok E, Gross WL, Kolaskar AS, Kulkarni-Kale U
Title Determination of primary amino acid sequence and unique three-dimensional structure of WGH1, a monoclonal human IgM antibody with anti-PR3 specificity.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10103046
Journal Eur J Biochem
Year 1999
Volume 261
Pages 155-62
Authors Goldmann WH, Niles JL, Arnaout MA
Title Interaction of purified human proteinase 3 (PR3) with reconstituted lipid bilayers.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 11094439
Journal Arthritis Res
Year 2000
Volume 2
Pages 263-7
Authors Specks U
Title What you should know about PR3-ANCA. Conformational requirements of proteinase 3 (PR3) for enzymatic activity and recognition by PR3-ANCA.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10976518
Journal Bioorg Med Chem
Year 2000
Volume 8
Pages 1713-7
Authors He S, Kuang R, Venkataraman R, Tu J, Truong TM, Chan HK, Groutas WC
Title Potent inhibition of serine proteases by heterocyclic sulfide derivatives of 1,2,5-thiadiazolidin-3-one 1,1 dioxide.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10975855
Journal J Immunol
Year 2000
Volume 165
Pages 3366-74
Authors Campbell EJ, Campbell MA, Owen CA
Title Bioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11159195
Journal Am J Pathol
Year 2001
Volume 158
Pages 581-92
Authors Yang JJ, Preston GA, Pendergraft WF, Segelmark M, Heeringa P, Hogan SL, Jennette JC, Falk RJ
Title Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generation of intracellular oxidants.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11747453
Journal Biochemistry
Year 2001
Volume 40
Pages 15762-70
Authors Cooley J, Takayama TK, Shapiro SD, Schechter NM, Remold-O'Donnell E
Title The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11408173
Journal Bioorg Med Chem
Year 2001
Volume 9
Pages 1543-8
Authors Groutas WC, He S, Kuang R, Ruan S, Tu J, Chan HK
Title Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 11168015
Journal Clin Exp Immunol
Year 2001
Volume 123
Pages 170-7
Authors Griffith ME, Coulthart A, Pemberton S, George AJ, Pusey CD
Title Anti-neutrophil cytoplasmic antibodies (ANCA) from patients with systemic vasculitis recognize restricted epitopes of proteinase 3 involving the catalytic site.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12135665
Journal Exp Hematol
Year 2002
Volume 30
Pages 689-96
Authors Skold S, Zeberg L, Gullberg U, Olofsson T
Title Functional dissociation between proforms and mature forms of proteinase 3, azurocidin, and granzyme B in regulation of granulopoiesis.
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the peptidase family-S1.
This enzyme has got a classical catalytic triad, composed of Ser/His/Asp, which is the same as that of trypsin (D00197 in EzCatDB). It suggests that it may have a similar catalytic mechanism to that of trypsin.

Created Updated
2004-10-29 2011-02-21