DB code: D00234

RLCP classification 1.13.10900.463 : Hydrolysis
CATH domain 3.10.170.10 : Elastase; domain 1 Catalytic domain
1.10.390.10 : Neutral Protease; domain 2 Catalytic domain
E.C. 3.4.24.27
CSA 1tlp 8tln
M-CSA 1tlp 8tln
MACiE M0176

CATH domain Related DB codes (homologues)
1.10.390.10 : Neutral Protease; domain 2 D00233 D00235 D00480
3.10.170.10 : Elastase; domain 1 D00233 D00235 D00480

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P00800 Thermolysin
EC 3.4.24.27
Thermostable neutral proteinase
M04.001 (Metallo)
PF07504 (FTP)
PF03413 (PepSY)
PF01447 (Peptidase_M4)
PF02868 (Peptidase_M4_C)
[Graphical View]

KEGG enzyme name
thermolysin
Bacillus thermoproteolyticus neutral proteinase
thermoase
thermoase Y10
TLN

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00800 THER_BACTH Preferential cleavage: Xaa-|-Leu > Xaa-|-Phe. Secreted. Binds 4 calcium ions per subunit. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00017 C00012 C00001 C00017 C00012
E.C.
Compound Zinc Protein Peptide H2O Protein Peptide(leaving group)
Type heavy metal peptide/protein peptide/protein H2O peptide/protein peptide/protein
ChEBI 29105
29105
15377
15377
PubChem 32051
32051
22247451
962
22247451
962
1fj3A01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1fjoA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1fjqA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1fjtA01 Bound:_ZN Unbound Unbound Bound:HOH_202 Unbound Bound:VAL-LYS Unbound
1fjuA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1fjvA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1fjwA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1gxwA01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-LYS Unbound
1hytA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:BZS
1keiA01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-LYS Unbound
1kjoA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-THR
1kjpA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-GLU
1kkkA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-ASP
1kl6A01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-ALA
1kr6A01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-DGL
1kroA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-DTH
1ks7A01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-DAS
1ktoA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-Analogue:PHQ-DAL
1l3fE01 Bound:_ZN_321 Unbound Unbound Unbound Unbound Unbound
1lnaE01 Analogue:_CO_900 Unbound Unbound Unbound Bound:VAL-LYS Unbound
1lnbE01 Analogue:_FE Unbound Unbound Unbound Bound:VAL-LYS Unbound
1lncE01 Analogue:_MN_900 Unbound Unbound Unbound Bound:VAL-LYS Unbound
1lndE01 Bound:_ZN_800 Unbound Unbound Unbound Bound:VAL-LYS Unbound
1lneE01 Analogue:_CD_900 Unbound Unbound Unbound Bound:VAL-LYS Unbound
1lnfE01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-LYS Unbound
1os0A01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PPH-DPH-PHE
1qf0A01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:TI2
1qf1A01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:TI1
1qf2A01 Bound:_ZN Unbound Analogue:TI3 Unbound Unbound Unbound
1thlA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:CLT-CCM-TRP
1tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
1tlpE01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:RHA-LEU-TRP
1tlxA01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-LYS Unbound
1tmnE01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:CLT-LEU-TRP
2tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
2tlxA01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-LYS Unbound
2tmnE01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PO3-LEU-NH2
3tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
3tlnA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
3tmnE01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-TRP Unbound
4tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
4tlnA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:LNO
4tmnE01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-PPH-LEU-ALA
5tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
5tlnA01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:BAN
5tmnE01 Bound:_ZN Unbound Unbound Unbound Unbound Transition-state-analogue:PHQ-PGL-LEU-LEU
6tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
6tmnE01 Bound:_ZN Unbound Unbound Unbound Unbound Intermediate-analogue:PHQ-PGL-1LU-LEU
7tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
7tlnA01 Bound:_ZN Unbound Unbound Unbound Unbound Intermediate-analogue:INC
8tliA01 Bound:_ZN Unbound Unbound Unbound Unbound Unbound
8tlnE01 Bound:_ZN Unbound Unbound Unbound Bound:VAL-LYS Unbound
1fj3A02 Unbound Unbound Unbound Unbound Unbound Unbound
1fjoA02 Unbound Unbound Unbound Unbound Unbound Unbound
1fjqA02 Unbound Unbound Unbound Unbound Unbound Unbound
1fjtA02 Unbound Unbound Unbound Unbound Unbound Unbound
1fjuA02 Unbound Unbound Unbound Unbound Unbound Unbound
1fjvA02 Unbound Unbound Unbound Unbound Unbound Unbound
1fjwA02 Unbound Unbound Unbound Unbound Unbound Unbound
1gxwA02 Unbound Unbound Unbound Unbound Unbound Unbound
1hytA02 Unbound Unbound Unbound Unbound Unbound Unbound
1keiA02 Unbound Unbound Unbound Unbound Unbound Unbound
1kjoA02 Unbound Unbound Unbound Unbound Unbound Unbound
1kjpA02 Unbound Unbound Unbound Unbound Unbound Unbound
1kkkA02 Unbound Unbound Unbound Unbound Unbound Unbound
1kl6A02 Unbound Unbound Unbound Unbound Unbound Unbound
1kr6A02 Unbound Unbound Unbound Unbound Unbound Unbound
1kroA02 Unbound Unbound Unbound Unbound Unbound Unbound
1ks7A02 Unbound Unbound Unbound Unbound Unbound Unbound
1ktoA02 Unbound Unbound Unbound Unbound Unbound Unbound
1l3fE02 Unbound Unbound Unbound Unbound Unbound Unbound
1lnaE02 Unbound Unbound Unbound Unbound Unbound Unbound
1lnbE02 Unbound Unbound Unbound Unbound Unbound Unbound
1lncE02 Unbound Unbound Unbound Unbound Unbound Unbound
1lndE02 Unbound Unbound Unbound Unbound Unbound Unbound
1lneE02 Unbound Unbound Unbound Unbound Unbound Unbound
1lnfE02 Unbound Unbound Unbound Unbound Unbound Unbound
1os0A02 Unbound Unbound Unbound Unbound Unbound Unbound
1qf0A02 Unbound Unbound Unbound Unbound Unbound Unbound
1qf1A02 Unbound Unbound Unbound Unbound Unbound Unbound
1qf2A02 Unbound Unbound Unbound Unbound Unbound Unbound
1thlA02 Unbound Unbound Unbound Unbound Unbound Unbound
1tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
1tlpE02 Unbound Unbound Unbound Unbound Unbound Unbound
1tlxA02 Unbound Unbound Unbound Unbound Unbound Unbound
1tmnE02 Unbound Unbound Unbound Unbound Unbound Unbound
1trlA Unbound Unbound Unbound Unbound Unbound Unbound
1trlB Unbound Unbound Unbound Unbound Unbound Unbound
2tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
2tlxA02 Unbound Unbound Unbound Unbound Unbound Unbound
2tmnE02 Unbound Unbound Unbound Unbound Unbound Unbound
3tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
3tlnA02 Unbound Unbound Unbound Unbound Unbound Unbound
3tmnE02 Unbound Unbound Unbound Unbound Unbound Unbound
4tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
4tlnA02 Unbound Unbound Unbound Unbound Unbound Unbound
4tmnE02 Unbound Unbound Unbound Unbound Unbound Unbound
5tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
5tlnA02 Unbound Unbound Unbound Unbound Unbound Unbound
5tmnE02 Unbound Unbound Unbound Unbound Unbound Unbound
6tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
6tmnE02 Unbound Unbound Unbound Unbound Unbound Unbound
7tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
7tlnA02 Unbound Unbound Unbound Unbound Unbound Unbound
8tliA02 Unbound Unbound Unbound Unbound Unbound Unbound
8tlnE02 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00800

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fj3A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fjoA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fjqA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fjtA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fjuA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fjvA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fjwA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1gxwA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1hytA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1keiA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1kjoA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1kjpA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1kkkA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1kl6A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1kr6A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1kroA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1ks7A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1ktoA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1l3fE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1lnaE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1lnbE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1lncE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1lndE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1lneE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1lnfE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1os0A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1qf0A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1qf1A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1qf2A01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1thlA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1tlpE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1tlxA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1tmnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
2tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
2tlxA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
2tmnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
3tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
3tlnA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
3tmnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
4tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
4tlnA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
4tmnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
5tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
5tlnA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
5tmnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
6tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
6tmnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
7tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
7tlnA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
8tliA01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
8tlnE01 ASN 112;GLU 143 HIS 142;HIS 146(Zinc binding) ALA 113
1fj3A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1fjoA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1fjqA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1fjtA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1fjuA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1fjvA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1fjwA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1gxwA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1hytA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1keiA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1kjoA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1kjpA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1kkkA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1kl6A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1kr6A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1kroA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1ks7A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1ktoA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1l3fE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1lnaE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1lnbE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1lncE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1lndE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1lneE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1lnfE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1os0A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1qf0A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1qf1A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1qf2A02 TYR 157;HIS 231 GLU 166(Zinc binding)
1thlA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1tlpE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1tlxA02 TYR 157;HIS 231 GLU 166(Zinc binding)
1tmnE02 TYR 157;HIS 231 GLU 166(Zinc binding)
1trlA
1trlB
2tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
2tlxA02 TYR 157;HIS 231 GLU 166(Zinc binding)
2tmnE02 TYR 157;HIS 231 GLU 166(Zinc binding)
3tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
3tlnA02 TYR 157;HIS 231 GLU 166(Zinc binding)
3tmnE02 TYR 157;HIS 231 GLU 166(Zinc binding)
4tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
4tlnA02 TYR 157;HIS 231 GLU 166(Zinc binding)
4tmnE02 TYR 157;HIS 231 GLU 166(Zinc binding)
5tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
5tlnA02 TYR 157;HIS 231 GLU 166(Zinc binding)
5tmnE02 TYR 157;HIS 231 GLU 166(Zinc binding)
6tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
6tmnE02 TYR 157;HIS 231 GLU 166(Zinc binding)
7tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
7tlnA02 TYR 157;HIS 231 GLU 166(Zinc binding)
8tliA02 TYR 157;HIS 231 GLU 166(Zinc binding)
8tlnE02 TYR 157;HIS 231 GLU 166(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig.5, p.6917-6920
[5]
[6]
p.5727-5728
[7]
[8]
Fig.1, p.8547-8549
[9]
[10]
p.3259
[17]
Fig.1, p.16807-16808
[20]
Scheme 1, p.7373
[42]
Fig.2, Fig.3, p.287-296

References
[1]
Resource
Comments ACTIVE SITE.
Medline ID 74052951
PubMed ID 4808703
Journal Biochemistry
Year 1974
Volume 13
Pages 205-10
Authors Burstein Y, Walsh KA, Neurath H
Title Evidence of an essential histidine residue in thermolysin
Related PDB
Related UniProtKB P00800
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 75041142
PubMed ID 4214815
Journal J Biol Chem
Year 1974
Volume 249
Pages 8030-44
Authors Matthews BW, Weaver LH, Kester WR
Title The conformation of thermolysin
Related PDB
Related UniProtKB P00800
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7317361
Journal Biochemistry
Year 1981
Volume 20
Pages 6912-20
Authors Holmes MA, Matthews BW
Title Binding of hydroxamic acid inhibitors to crystalline thermolysin suggests a pentacoordinate zinc intermediate in catalysis
Related PDB 4tln 5tln
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID 83085812
PubMed ID 7175940
Journal J Mol Biol
Year 1982
Volume 160
Pages 623-39
Authors Holmes MA, Matthews BW
Title Structure of thermolysin refined at 1.6 A resolution
Related PDB
Related UniProtKB P00800
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 6830761
Journal Biochemistry
Year 1983
Volume 22
Pages 236-40
Authors Holmes MA, Tronrud DE, Matthews BW
Title Structural analysis of the inhibition of thermolysin by an active-site-directed irreversible inhibitor
Related PDB 7tln
Related UniProtKB
[6]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 6395881
Journal Biochemistry
Year 1984
Volume 23
Pages 5724-9
Authors Monzingo AF, Matthews BW
Title Binding of N-carboxymethyl dipeptide inhibitors to thermolysin determined by X-ray crystallography: a novel class of transition-state analogues for zinc peptidases
Related PDB 1tmn
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 3709536
Journal Eur J Biochem
Year 1986
Volume 157
Pages 261-8
Authors Tronrud DE, Monzingo AF, Matthews BW
Title Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin
Related PDB 1tlp 2tmn
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 3442675
Journal Biochemistry
Year 1987
Volume 26
Pages 8542-53
Authors Holden HM, Tronrud DE, Monzingo AF, Weaver LH, Matthews BW
Title Slow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues
Related PDB 4tmn 5tmn
Related UniProtKB
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 3810156
Journal Science
Year 1987
Volume 235
Pages 571-4
Authors Tronrud DE, Holden HM, Matthews BW
Title Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond
Related PDB 6tmn
Related UniProtKB
[10]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 3343246
Journal J Biol Chem
Year 1988
Volume 263
Pages 3256-60
Authors Holden HM, Matthews BW
Title The binding of L-valyl-L-tryptophan to crystalline thermolysin illustrates the mode of interaction of a product of peptide hydrolysis
Related PDB 3tmn
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2019475
Journal Int J Pept Protein Res
Year 1991
Volume 37
Pages 128-33
Authors Miranda MT, Tominaga M
Title Thermolysin as a catalyst in enzymatic synthesis of asparagine-containing peptides II
Related PDB
Related UniProtKB
[12]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 1445869
Journal Biochemistry
Year 1992
Volume 31
Pages 11310-6
Authors Holland DR, Tronrud DE, Pley HW, Flaherty KM, Stark W, Jansonius JN, McKay DB, Matthews BW
Title Structural comparison suggests that thermolysin and related neutral proteases undergo hinge-bending motion during catalysis
Related PDB 3tln 8tln
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8286362
Journal Biochemistry
Year 1994
Volume 33
Pages 51-6
Authors Holland DR, Barclay PL, Danilewicz JC, Matthews BW, James K
Title Inhibition of thermolysin and neutral endopeptidase 24.11 by a novel glutaramide derivative: X-ray structure determination of the thermolysin-inhibitor complex
Related PDB 1thl
Related UniProtKB
[14]
Resource
Comments STRUCTURE BY NMR OF 487-548.
Medline ID 95086079
PubMed ID 7993910
Journal Biochemistry
Year 1994
Volume 33
Pages 14834-47
Authors Rico M, Jimenez MA, Gonzalez C, De Filippis V, Fontana A
Title NMR solution structure of the C-terminal fragment 255-316 of thermolysin: a dimer formed by subunits having the native structure
Related PDB 1trl
Related UniProtKB P00800
[15]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8034637
Journal J Biol Chem
Year 1994
Volume 269
Pages 18839-42
Authors Hausrath AC, Matthews BW
Title Redetermination and refinement of the complex of benzylsuccinic acid with thermolysin and its relation to the complex with carboxypeptidase A
Related PDB 1hyt
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 7720870
Journal FEBS Lett
Year 1995
Volume 362
Pages 189-91
Authors Kunugi S, Yokoyama M, Sakamoto A
Title Observation of the pre-steady state process in thermolysin catalysis with a fluorescent displacement probe at low pH
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 7622493
Journal J Biol Chem
Year 1995
Volume 270
Pages 16803-8
Authors Beaumont A, O'Donohue MJ, Paredes N, Rousselet N, Assicot M, Bohuon C, Fournie-Zaluski MC, Roques BP
Title The role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 7629812
Journal J Med Chem
Year 1995
Volume 38
Pages 2742-7
Authors Beusen DD, McDowell LM, Slomczynska U, Schaefer J
Title Solid-state nuclear magnetic resonance analysis of the conformation of an inhibitor bound to thermolysin
Related PDB
Related UniProtKB
[19]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8535232
Journal Protein Sci
Year 1995
Volume 4
Pages 1955-65
Authors Holland DR, Hausrath AC, Juers D, Matthews BW
Title Structural analysis of zinc substitutions in the active site of thermolysin
Related PDB 1lna 1lnb 1lnc 1lnd 1lne 1lnf
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 8652513
Journal Biochemistry
Year 1996
Volume 35
Pages 7369-77
Authors Mock WL, Stanford DJ
Title Arazoformyl dipeptide substrates for thermolysin. Confirmation of a reverse protonation catalytic mechanism
Related PDB
Related UniProtKB
[21]
Resource
Comments STRUCTURE BY NMR OF 437-548.
Medline ID 97452621
PubMed ID 9305992
Journal Biochemistry
Year 1997
Volume 36
Pages 11975-83
Authors Conejero-Lara F, Gonzalez C, Jimenez MA, Padmanabhan S, Mateo PL, Rico M
Title NMR solution structure of the 205-316 C-terminal fragment of thermolysin. An example of dimerization coupled to partial unfolding
Related PDB
Related UniProtKB P00800
[22]
Resource
Comments
Medline ID
PubMed ID 9262642
Journal J Pept Sci
Year 1997
Volume 3
Pages 245-51
Authors Eichhorn U, Bommarius AS, Drauz K, Jakubke HD
Title Synthesis of dipeptides by suspension-to-suspension conversion via thermolysin catalysis: from analytical to preparative scale
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[23]
Resource
Comments
Medline ID
PubMed ID 9153087
Journal Protein Eng
Year 1997
Volume 10
Pages 223-30
Authors Frigerio F, Margarit I, Nogarotto R, Grandi G, Vriend G, Hardy F, Veltman OR, Venema G, Eijsink VG
Title Model building of a thermolysin-like protease by mutagenesis.
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[24]
Resource
Comments
Medline ID
PubMed ID 9928125
Journal Ann N Y Acad Sci
Year 1998
Volume 864
Pages 458-62
Authors Pauthe E, Dauchez M, Berry H, Berjot M, Monti JP, Alix AJ, Larreta-Garde V
Title Enzymatic and structural approaches of the thermolysin mechanism in glycerol-containing media
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[25]
Resource
Comments
Medline ID
PubMed ID 10099304
Journal Biotechnol Bioeng
Year 1998
Volume 58
Pages 654-7
Authors Bedell BA, Mozhaev VV, Clark DS, Dordick JS
Title Testing for diffusion limitations in salt-activated enzyme catalysts operating in organic solvents
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[26]
Resource
Comments
Medline ID
PubMed ID 9488701
Journal J Biol Chem
Year 1998
Volume 273
Pages 5697-701
Authors Marie-Claire C, Roques BP, Beaumont A
Title Intramolecular processing of prothermolysin
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[27]
Resource
Comments
Medline ID
PubMed ID 9735298
Journal J Mol Biol
Year 1998
Volume 282
Pages 435-46
Authors Tate S, Ohno A, Seeram SS, Hiraga K, Oda K, Kainosho M
Title Elucidation of the mode of interaction of thermolysin with a proteinaceous metalloproteinase inhibitor, SMPI, based on a model complex structure and a structural dynamics analysis
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[28]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10504225
Journal Biochemistry
Year 1999
Volume 38
Pages 12569-76
Authors Gaucher JF, Selkti M, Tiraboschi G, Prange T, Roques BP, Tomas A, Fournie-Zaluski MC
Title Crystal structures of alpha-mercaptoacyldipeptides in the thermolysin active site: structural parameters for a Zn monodentation or bidentation in metalloendopeptidases
Related PDB 1qf0 1qf1 1qf2
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[29]
Resource
Comments
Medline ID
PubMed ID 10467116
Journal Biotechnol Appl Biochem
Year 1999
Volume 30
Pages 35-40
Authors Van den Burg B, de Kreij A, Van der Veek P, Mansfeld J, Venema G
Title Characterization of a novel stable biocatalyst obtained by protein engineering.
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[30]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10651278
Journal Proteins
Year 1999
Volume 37
Pages 628-40
Authors English AC, Done SH, Caves LS, Groom CR, Hubbard RE
Title Locating interaction sites on proteins: the crystal structure of thermolysin soaked in 2% to 100% isopropanol
Related PDB 1tli 1tlx 2tlx 2tli 3tli 4tli 5tli 6tli 7tli 8tli
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[31]
Resource
Comments
Medline ID
PubMed ID 10869357
Journal J Biol Chem
Year 2000
Volume 275
Pages 31115-20
Authors de Kreij A, Venema G, van den Burg B
Title Substrate specificity in the highly heterogeneous M4 peptidase family is determined by a small subset of amino acids.
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[32]
Resource
Comments
Medline ID
PubMed ID 10921773
Journal J Comput Aided Mol Des
Year 2000
Volume 14
Pages 573-91
Authors Cosgrove DA, Bayada DM, Johnson AP
Title A novel method of aligning molecules by local surface shape similarity
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[33]
Resource
Comments
Medline ID
PubMed ID 11326120
Journal Acta Crystallogr A
Year 2001
Volume 57
Pages 351-8
Authors Webster G, Hilgenfeld R
Title An evolutionary computational approach to the phase problem in macromolecular X-ray crystallography
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[34]
Resource
Comments
Medline ID
PubMed ID 11427942
Journal Biotechnol Bioeng
Year 2001
Volume 74
Pages 406-15
Authors Murakami Y, Chiba K, Oda T, Hirata A
Title Novel kinetic analysis of enzymatic dipeptide synthesis: effect of pH and substrates on thermolysin catalysis
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[35]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11287678
Journal Protein Eng
Year 2001
Volume 14
Pages 47-59
Authors English AC, Groom CR, Hubbard RE
Title Experimental and computational mapping of the binding surface of a crystalline protein
Related PDB 1fj3 1fjo 1fjq 1fjt 1fju 1fjv 1fjw
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[36]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12454500
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 2198-200
Authors Gaucher JF, Selkti M, Prange T, Tomas A
Title The 2.2 A resolution structure of thermolysin (TLN) crystallized in the presence of potassium thiocyanate.
Related PDB 1gxw
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[37]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12037302
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 1002-7
Authors Hausrath AC, Matthews BW
Title Thermolysin in the absence of substrate has an open conformation
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[38]
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Comments
Medline ID
PubMed ID 12023041
Journal FEBS Lett
Year 2002
Volume 519
Pages 181-4
Authors Pedersen NR, Halling PJ, Pedersen LH, Wimmer R, Matthiesen R, Veltman OR
Title Efficient transesterification of sucrose catalysed by the metalloprotease thermolysin in dimethylsulfoxide
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[39]
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Comments
Medline ID
PubMed ID 11996551
Journal J Am Chem Soc
Year 2002
Volume 124
Pages 5254-5
Authors Rich JO, Mozhaev VV, Dordick JS, Clark DS, Khmelnitsky YL
Title Molecular imprinting of enzymes with water-insoluble ligands for nonaqueous biocatalysis
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[40]
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Comments
Medline ID
PubMed ID 11859085
Journal J Biol Chem
Year 2002
Volume 277
Pages 15432-8
Authors de Kreij A, van den Burg B, Venema G, Vriend G, Eijsink VG, Nielsen JE
Title The effects of modifying the surface charge on the catalytic activity of a thermolysin-like protease.
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[41]
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Comments
Medline ID
PubMed ID 11935352
Journal J Biol Inorg Chem
Year 2002
Volume 7
Pages 284-98
Authors Pelmenschikov V, Blomberg MR, Siegbahn PE
Title A theoretical study of the mechanism for peptide hydrolysis by thermolysin.
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[42]
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Comments
Medline ID
PubMed ID 11858637
Journal J Mol Graph Model
Year 2002
Volume 20
Pages 281-95
Authors Clark RD, Strizhev A, Leonard JM, Blake JF, Matthew JB
Title Consensus scoring for ligand/protein interactions
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[43]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12832763
Journal Acta Crystallogr D Biol Crystallogr
Year 2003
Volume 59
Pages 1200-5
Authors Selkti M, Tomas A, Gaucher JF, Prange T, Fournie-Zaluski MC, Chen H, Roques BP
Title Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.
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[44]
Resource
Comments
Medline ID
PubMed ID 12569506
Journal Angew Chem Int Ed Engl
Year 2003
Volume 42
Pages 421-4
Authors Kelso MJ, Hoang HN, Oliver W, Sokolenko N, March DR, Appleton TG, Fairlie DP
Title A cyclic metallopeptide induces alpha helicity in short peptide fragments of thermolysin.
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[45]
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Comments
Medline ID
PubMed ID 12735988
Journal Bioorg Med Chem
Year 2003
Volume 11
Pages 2421-6
Authors Kim SJ, Kim DH, Park JD, Woo JR, Jin Y, Ryu SE
Title Origin of the stereospecificity in binding hydroxamates of alpha- and beta-phenylalanine methylamide to thermolysin revealed by the X-ray crystallographic study.
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Comments
This enzyme belongs to peptidase family-M4 (Thermolysin family).
Although this enzyme binds four calcium ions, they are not involved in catalysis.
According to the literature [8], the catalytic reaction proceeds as follows:
(1) Carbonyl oxygen of Target bond and hydrorytic water molecule are bound to zinc ion, which facilitates the catalysis. Glu143 acts as a general base to deprotonate and activate the water molecule.
(2) The water molecule makes a nucleophilic attack on the carbonyl carbon to form a tetrahedral intermediate.
(3) The intermediate is stabilized by His231, Tyr157, Asn112 and mainchain carbonyl of Ala113, together with the zinc ion. Here, His231 and Tyr157 stabilize the negative charge on the hydroxyl anion (originally carbonyl oxygen), whereas Asn112 and mainchain carbonyl group of Ala113 stabilize the leaving amine group. The zinc ion stabilizes the negative charge on the hydroxyl anion and the new hydroxyl group (originally water).
(4) Glu143 acts as a genral acid to protonate the leaving amine group. (Glu143 may also shuttle the remaining proton from the hydroxyl group to the amine to complete the bond cleavage.)

Created Updated
2005-04-01 2009-03-16