EzCatDB: D00234

DB codeD00234
RLCP classification1.13.10900.463
CATH domainDomain 13.10.170.10Catalytic domain
Domain 21.10.390.10Catalytic domain
E.C.3.4.24.27
CSA1tlp,8tln
MACiEM0176

CATH domainRelated DB codes (homologues)
1.10.390.10D00233,D00235,D00480
3.10.170.10D00233,D00235,D00480

Enzyme Name
Swiss-protKEGG

P00800
Protein nameThermolysinthermolysin
Bacillus thermoproteolyticus neutral proteinase
thermoase
thermoase Y10
TLN
SynonymsEC 3.4.24.27
Thermostable neutral proteinase


Swiss-prot:Accession NumberP00800
Entry nameTHER_BACTH
ActivityPreferential cleavage: Xaa-|-Leu > Xaa-|-Phe.
Subunit
Subcellular locationSecreted.
CofactorBinds 4 calcium ions per subunit.,Binds 1 zinc ion per subunit.


CofactorsSubstratesProductsintermediates
KEGG-idC00038C00017C00012C00001C00017C00012
CompoundZincProteinPeptideH2OProteinPeptide(leaving group)
Typeheavy metalpeptide/proteinpeptide/proteinH2Opeptide/proteinpeptide/protein
1fj3A01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1fjoA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1fjqA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1fjtA01Bound:_ZNUnboundUnboundBound:HOH 202UnboundBound:VAL-LYSUnbound
1fjuA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1fjvA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1fjwA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1gxwA01Bound:_ZNUnboundUnbound
UnboundBound:VAL-LYSUnbound
1hytA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:BZS
1keiA01Bound:_ZNUnboundUnbound
UnboundBound:VAL-LYSUnbound
1kjoA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-THR
1kjpA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-GLU
1kkkA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-ASP
1kl6A01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-ALA
1kr6A01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-DGL
1kroA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-DTH
1ks7A01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-DAS
1ktoA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-Analogue:PHQ-DAL
1l3fE01Bound:_ZN 321UnboundUnbound
UnboundUnboundUnbound
1lnaE01Analogue:_CO 900UnboundUnbound
UnboundBound:VAL-LYSUnbound
1lnbE01Analogue:_FEUnboundUnbound
UnboundBound:VAL-LYSUnbound
1lncE01Analogue:_MN 900UnboundUnbound
UnboundBound:VAL-LYSUnbound
1lndE01Bound:_ZN 800UnboundUnbound
UnboundBound:VAL-LYSUnbound
1lneE01Analogue:_CD 900UnboundUnbound
UnboundBound:VAL-LYSUnbound
1lnfE01Bound:_ZNUnboundUnbound
UnboundBound:VAL-LYSUnbound
1os0A01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PPH-DPH-PHE
1qf0A01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:TI2
1qf1A01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:TI1
1qf2A01Bound:_ZNUnboundAnalogue:TI3
UnboundUnboundUnbound
1thlA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:CLT-CCM-TRP
1tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
1tlpE01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:RHA-LEU-TRP
1tlxA01Bound:_ZNUnboundUnbound
UnboundBound:VAL-LYSUnbound
1tmnE01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:CLT-LEU-TRP
2tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
2tlxA01Bound:_ZNUnboundUnbound
UnboundBound:VAL-LYSUnbound
2tmnE01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PO3-LEU-NH2
3tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
3tlnA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
3tmnE01Bound:_ZNUnboundUnbound
UnboundBound:VAL-TRPUnbound
4tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
4tlnA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:LNO
4tmnE01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-PPH-LEU-ALA
5tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
5tlnA01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:BAN
5tmnE01Bound:_ZNUnboundUnbound
UnboundUnboundTransition-state-analogue:PHQ-PGL-LEU-LEU
6tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
6tmnE01Bound:_ZNUnboundUnbound
UnboundUnboundIntermediate-analogue:PHQ-PGL-1LU-LEU
7tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
7tlnA01Bound:_ZNUnboundUnbound
UnboundUnboundIntermediate-analogue:INC
8tliA01Bound:_ZNUnboundUnbound
UnboundUnboundUnbound
8tlnE01Bound:_ZNUnboundUnbound
UnboundBound:VAL-LYSUnbound
1fj3A02UnboundUnboundUnbound
UnboundUnboundUnbound
1fjoA02UnboundUnboundUnbound
UnboundUnboundUnbound
1fjqA02UnboundUnboundUnbound
UnboundUnboundUnbound
1fjtA02UnboundUnboundUnbound
UnboundUnboundUnbound
1fjuA02UnboundUnboundUnbound
UnboundUnboundUnbound
1fjvA02UnboundUnboundUnbound
UnboundUnboundUnbound
1fjwA02UnboundUnboundUnbound
UnboundUnboundUnbound
1gxwA02UnboundUnboundUnbound
UnboundUnboundUnbound
1hytA02UnboundUnboundUnbound
UnboundUnboundUnbound
1keiA02UnboundUnboundUnbound
UnboundUnboundUnbound
1kjoA02UnboundUnboundUnbound
UnboundUnboundUnbound
1kjpA02UnboundUnboundUnbound
UnboundUnboundUnbound
1kkkA02UnboundUnboundUnbound
UnboundUnboundUnbound
1kl6A02UnboundUnboundUnbound
UnboundUnboundUnbound
1kr6A02UnboundUnboundUnbound
UnboundUnboundUnbound
1kroA02UnboundUnboundUnbound
UnboundUnboundUnbound
1ks7A02UnboundUnboundUnbound
UnboundUnboundUnbound
1ktoA02UnboundUnboundUnbound
UnboundUnboundUnbound
1l3fE02UnboundUnboundUnbound
UnboundUnboundUnbound
1lnaE02UnboundUnboundUnbound
UnboundUnboundUnbound
1lnbE02UnboundUnboundUnbound
UnboundUnboundUnbound
1lncE02UnboundUnboundUnbound
UnboundUnboundUnbound
1lndE02UnboundUnboundUnbound
UnboundUnboundUnbound
1lneE02UnboundUnboundUnbound
UnboundUnboundUnbound
1lnfE02UnboundUnboundUnbound
UnboundUnboundUnbound
1os0A02UnboundUnboundUnbound
UnboundUnboundUnbound
1qf0A02UnboundUnboundUnbound
UnboundUnboundUnbound
1qf1A02UnboundUnboundUnbound
UnboundUnboundUnbound
1qf2A02UnboundUnboundUnbound
UnboundUnboundUnbound
1thlA02UnboundUnboundUnbound
UnboundUnboundUnbound
1tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
1tlpE02UnboundUnboundUnbound
UnboundUnboundUnbound
1tlxA02UnboundUnboundUnbound
UnboundUnboundUnbound
1tmnE02UnboundUnboundUnbound
UnboundUnboundUnbound
1trlAUnboundUnboundUnbound
UnboundUnboundUnbound
1trlBUnboundUnboundUnbound
UnboundUnboundUnbound
2tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
2tlxA02UnboundUnboundUnbound
UnboundUnboundUnbound
2tmnE02UnboundUnboundUnbound
UnboundUnboundUnbound
3tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
3tlnA02UnboundUnboundUnbound
UnboundUnboundUnbound
3tmnE02UnboundUnboundUnbound
UnboundUnboundUnbound
4tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
4tlnA02UnboundUnboundUnbound
UnboundUnboundUnbound
4tmnE02UnboundUnboundUnbound
UnboundUnboundUnbound
5tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
5tlnA02UnboundUnboundUnbound
UnboundUnboundUnbound
5tmnE02UnboundUnboundUnbound
UnboundUnboundUnbound
6tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
6tmnE02UnboundUnboundUnbound
UnboundUnboundUnbound
7tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
7tlnA02UnboundUnboundUnbound
UnboundUnboundUnbound
8tliA02UnboundUnboundUnbound
UnboundUnboundUnbound
8tlnE02UnboundUnboundUnbound
UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00800
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
1fj3A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fjoA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fjqA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fjtA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fjuA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fjvA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fjwA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1gxwA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1hytA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1keiA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1kjoA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1kjpA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1kkkA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1kl6A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1kr6A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1kroA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1ks7A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1ktoA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1l3fE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1lnaE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1lnbE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1lncE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1lndE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1lneE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1lnfE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1os0A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1qf0A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1qf1A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1qf2A01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1thlA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1tlpE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1tlxA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1tmnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
2tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
2tlxA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
2tmnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
3tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
3tlnA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
3tmnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
4tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
4tlnA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
4tmnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
5tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
5tlnA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
5tmnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
6tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
6tmnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
7tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
7tlnA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
8tliA01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
8tlnE01ASN 112;GLU 143
HIS 142;HIS 146(Zinc binding)
ALA 113
1fj3A02TYR 157;HIS 231
GLU 166(Zinc binding)

1fjoA02TYR 157;HIS 231
GLU 166(Zinc binding)

1fjqA02TYR 157;HIS 231
GLU 166(Zinc binding)

1fjtA02TYR 157;HIS 231
GLU 166(Zinc binding)

1fjuA02TYR 157;HIS 231
GLU 166(Zinc binding)

1fjvA02TYR 157;HIS 231
GLU 166(Zinc binding)

1fjwA02TYR 157;HIS 231
GLU 166(Zinc binding)

1gxwA02TYR 157;HIS 231
GLU 166(Zinc binding)

1hytA02TYR 157;HIS 231
GLU 166(Zinc binding)

1keiA02TYR 157;HIS 231
GLU 166(Zinc binding)

1kjoA02TYR 157;HIS 231
GLU 166(Zinc binding)

1kjpA02TYR 157;HIS 231
GLU 166(Zinc binding)

1kkkA02TYR 157;HIS 231
GLU 166(Zinc binding)

1kl6A02TYR 157;HIS 231
GLU 166(Zinc binding)

1kr6A02TYR 157;HIS 231
GLU 166(Zinc binding)

1kroA02TYR 157;HIS 231
GLU 166(Zinc binding)

1ks7A02TYR 157;HIS 231
GLU 166(Zinc binding)

1ktoA02TYR 157;HIS 231
GLU 166(Zinc binding)

1l3fE02TYR 157;HIS 231
GLU 166(Zinc binding)

1lnaE02TYR 157;HIS 231
GLU 166(Zinc binding)

1lnbE02TYR 157;HIS 231
GLU 166(Zinc binding)

1lncE02TYR 157;HIS 231
GLU 166(Zinc binding)

1lndE02TYR 157;HIS 231
GLU 166(Zinc binding)

1lneE02TYR 157;HIS 231
GLU 166(Zinc binding)

1lnfE02TYR 157;HIS 231
GLU 166(Zinc binding)

1os0A02TYR 157;HIS 231
GLU 166(Zinc binding)

1qf0A02TYR 157;HIS 231
GLU 166(Zinc binding)

1qf1A02TYR 157;HIS 231
GLU 166(Zinc binding)

1qf2A02TYR 157;HIS 231
GLU 166(Zinc binding)

1thlA02TYR 157;HIS 231
GLU 166(Zinc binding)

1tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

1tlpE02TYR 157;HIS 231
GLU 166(Zinc binding)

1tlxA02TYR 157;HIS 231
GLU 166(Zinc binding)

1tmnE02TYR 157;HIS 231
GLU 166(Zinc binding)

1trlA


1trlB


2tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

2tlxA02TYR 157;HIS 231
GLU 166(Zinc binding)

2tmnE02TYR 157;HIS 231
GLU 166(Zinc binding)

3tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

3tlnA02TYR 157;HIS 231
GLU 166(Zinc binding)

3tmnE02TYR 157;HIS 231
GLU 166(Zinc binding)

4tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

4tlnA02TYR 157;HIS 231
GLU 166(Zinc binding)

4tmnE02TYR 157;HIS 231
GLU 166(Zinc binding)

5tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

5tlnA02TYR 157;HIS 231
GLU 166(Zinc binding)

5tmnE02TYR 157;HIS 231
GLU 166(Zinc binding)

6tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

6tmnE02TYR 157;HIS 231
GLU 166(Zinc binding)

7tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

7tlnA02TYR 157;HIS 231
GLU 166(Zinc binding)

8tliA02TYR 157;HIS 231
GLU 166(Zinc binding)

8tlnE02TYR 157;HIS 231
GLU 166(Zinc binding)


References for Catalytic Mechanism
ReferencesSectionsNo. 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]
CommentsACTIVE SITE.
Medline ID74052951
PubMed ID4808703
JournalBiochemistry
Year1974
Volume13
Pages205-10
AuthorsBurstein Y, Walsh KA, Neurath H
TitleEvidence of an essential histidine residue in thermolysin
Related Swiss-protP00800
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID75041142
PubMed ID4214815
JournalJ Biol Chem
Year1974
Volume249
Pages8030-44
AuthorsMatthews BW, Weaver LH, Kester WR
TitleThe conformation of thermolysin
Related Swiss-protP00800
[3]
CommentsX-ray crystallography
PubMed ID7317361
JournalBiochemistry
Year1981
Volume20
Pages6912-20
AuthorsHolmes MA, Matthews BW
TitleBinding of hydroxamic acid inhibitors to crystalline thermolysin suggests a pentacoordinate zinc intermediate in catalysis
Related PDB4tln,5tln
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID83085812
PubMed ID7175940
JournalJ Mol Biol
Year1982
Volume160
Pages623-39
AuthorsHolmes MA, Matthews BW
TitleStructure of thermolysin refined at 1.6 A resolution
Related Swiss-protP00800
[5]
CommentsX-ray crystallography
PubMed ID6830761
JournalBiochemistry
Year1983
Volume22
Pages236-40
AuthorsHolmes MA, Tronrud DE, Matthews BW
TitleStructural analysis of the inhibition of thermolysin by an active-site-directed irreversible inhibitor
Related PDB7tln
[6]
CommentsX-ray crystallography
PubMed ID6395881
JournalBiochemistry
Year1984
Volume23
Pages5724-9
AuthorsMonzingo AF, Matthews BW
TitleBinding of N-carboxymethyl dipeptide inhibitors to thermolysin determined by X-ray crystallography: a novel class of transition-state analogues for zinc peptidases
Related PDB1tmn
[7]
CommentsX-ray crystallography
PubMed ID3709536
JournalEur J Biochem
Year1986
Volume157
Pages261-8
AuthorsTronrud DE, Monzingo AF, Matthews BW
TitleCrystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin
Related PDB1tlp,2tmn
[8]
CommentsX-ray crystallography
PubMed ID3442675
JournalBiochemistry
Year1987
Volume26
Pages8542-53
AuthorsHolden HM, Tronrud DE, Monzingo AF, Weaver LH, Matthews BW
TitleSlow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues
Related PDB4tmn,5tmn
[9]
CommentsX-ray crystallography
PubMed ID3810156
JournalScience
Year1987
Volume235
Pages571-4
AuthorsTronrud DE, Holden HM, Matthews BW
TitleStructures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond
Related PDB6tmn
[10]
CommentsX-ray crystallography
PubMed ID3343246
JournalJ Biol Chem
Year1988
Volume263
Pages3256-60
AuthorsHolden HM, Matthews BW
TitleThe binding of L-valyl-L-tryptophan to crystalline thermolysin illustrates the mode of interaction of a product of peptide hydrolysis
Related PDB3tmn
[11]
PubMed ID2019475
JournalInt J Pept Protein Res
Year1991
Volume37
Pages128-33
AuthorsMiranda MT, Tominaga M
TitleThermolysin as a catalyst in enzymatic synthesis of asparagine-containing peptides II
[12]
CommentsX-ray crystallography
PubMed ID1445869
JournalBiochemistry
Year1992
Volume31
Pages11310-6
AuthorsHolland DR, Tronrud DE, Pley HW, Flaherty KM, Stark W, Jansonius JN, McKay DB, Matthews BW
TitleStructural comparison suggests that thermolysin and related neutral proteases undergo hinge-bending motion during catalysis
Related PDB3tln,8tln
[13]
PubMed ID8286362
JournalBiochemistry
Year1994
Volume33
Pages51-6
AuthorsHolland DR, Barclay PL, Danilewicz JC, Matthews BW, James K
TitleInhibition of thermolysin and neutral endopeptidase 24.11 by a novel glutaramide derivative: X-ray structure determination of the thermolysin-inhibitor complex
Related PDB1thl
[14]
CommentsSTRUCTURE BY NMR OF 487-548.
Medline ID95086079
PubMed ID7993910
JournalBiochemistry
Year1994
Volume33
Pages14834-47
AuthorsRico M, Jimenez MA, Gonzalez C, De Filippis V, Fontana A
TitleNMR solution structure of the C-terminal fragment 255-316 of thermolysin: a dimer formed by subunits having the native structure
Related PDB1trl
Related Swiss-protP00800
[15]
CommentsX-ray crystallography
PubMed ID8034637
JournalJ Biol Chem
Year1994
Volume269
Pages18839-42
AuthorsHausrath AC, Matthews BW
TitleRedetermination and refinement of the complex of benzylsuccinic acid with thermolysin and its relation to the complex with carboxypeptidase A
Related PDB1hyt
[16]
PubMed ID7720870
JournalFEBS Lett
Year1995
Volume362
Pages189-91
AuthorsKunugi S, Yokoyama M, Sakamoto A
TitleObservation of the pre-steady state process in thermolysin catalysis with a fluorescent displacement probe at low pH
[17]
PubMed ID7622493
JournalJ Biol Chem
Year1995
Volume270
Pages16803-8
AuthorsBeaumont A, O'Donohue MJ, Paredes N, Rousselet N, Assicot M, Bohuon C, Fournie-Zaluski MC, Roques BP
TitleThe role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study
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PubMed ID7629812
JournalJ Med Chem
Year1995
Volume38
Pages2742-7
AuthorsBeusen DD, McDowell LM, Slomczynska U, Schaefer J
TitleSolid-state nuclear magnetic resonance analysis of the conformation of an inhibitor bound to thermolysin
[19]
CommentsX-ray crystallography
PubMed ID8535232
JournalProtein Sci
Year1995
Volume4
Pages1955-65
AuthorsHolland DR, Hausrath AC, Juers D, Matthews BW
TitleStructural analysis of zinc substitutions in the active site of thermolysin
Related PDB1lna,1lnb,1lnc,1lnd,1lne,1lnf
[20]
PubMed ID8652513
JournalBiochemistry
Year1996
Volume35
Pages7369-77
AuthorsMock WL, Stanford DJ
TitleArazoformyl dipeptide substrates for thermolysin. Confirmation of a reverse protonation catalytic mechanism
[21]
CommentsSTRUCTURE BY NMR OF 437-548.
Medline ID97452621
PubMed ID9305992
JournalBiochemistry
Year1997
Volume36
Pages11975-83
AuthorsConejero-Lara F, Gonzalez C, Jimenez MA, Padmanabhan S, Mateo PL, Rico M
TitleNMR solution structure of the 205-316 C-terminal fragment of thermolysin. An example of dimerization coupled to partial unfolding
Related Swiss-protP00800
[22]
PubMed ID9262642
JournalJ Pept Sci
Year1997
Volume3
Pages245-51
AuthorsEichhorn U, Bommarius AS, Drauz K, Jakubke HD
TitleSynthesis of dipeptides by suspension-to-suspension conversion via thermolysin catalysis: from analytical to preparative scale
[23]
PubMed ID9153087
JournalProtein Eng
Year1997
Volume10
Pages223-30
AuthorsFrigerio F, Margarit I, Nogarotto R, Grandi G, Vriend G, Hardy F, Veltman OR, Venema G, Eijsink VG
TitleModel building of a thermolysin-like protease by mutagenesis.
[24]
PubMed ID9928125
JournalAnn N Y Acad Sci
Year1998
Volume864
Pages458-62
AuthorsPauthe E, Dauchez M, Berry H, Berjot M, Monti JP, Alix AJ, Larreta-Garde V
TitleEnzymatic and structural approaches of the thermolysin mechanism in glycerol-containing media
[25]
PubMed ID10099304
JournalBiotechnol Bioeng
Year1998
Volume58
Pages654-7
AuthorsBedell BA, Mozhaev VV, Clark DS, Dordick JS
TitleTesting for diffusion limitations in salt-activated enzyme catalysts operating in organic solvents
[26]
PubMed ID9488701
JournalJ Biol Chem
Year1998
Volume273
Pages5697-701
AuthorsMarie-Claire C, Roques BP, Beaumont A
TitleIntramolecular processing of prothermolysin
[27]
PubMed ID9735298
JournalJ Mol Biol
Year1998
Volume282
Pages435-46
AuthorsTate S, Ohno A, Seeram SS, Hiraga K, Oda K, Kainosho M
TitleElucidation of the mode of interaction of thermolysin with a proteinaceous metalloproteinase inhibitor, SMPI, based on a model complex structure and a structural dynamics analysis
[28]
CommentsX-ray crystallography
PubMed ID10504225
JournalBiochemistry
Year1999
Volume38
Pages12569-76
AuthorsGaucher JF, Selkti M, Tiraboschi G, Prange T, Roques BP, Tomas A, Fournie-Zaluski MC
TitleCrystal structures of alpha-mercaptoacyldipeptides in the thermolysin active site: structural parameters for a Zn monodentation or bidentation in metalloendopeptidases
Related PDB1qf0,1qf1,1qf2
[29]
PubMed ID10467116
JournalBiotechnol Appl Biochem
Year1999
Volume30
Pages35-40
AuthorsVan den Burg B, de Kreij A, Van der Veek P, Mansfeld J, Venema G
TitleCharacterization of a novel stable biocatalyst obtained by protein engineering.
[30]
CommentsX-ray crystallography
PubMed ID10651278
JournalProteins
Year1999
Volume37
Pages628-40
AuthorsEnglish AC, Done SH, Caves LS, Groom CR, Hubbard RE
TitleLocating interaction sites on proteins: the crystal structure of thermolysin soaked in 2% to 100% isopropanol
Related PDB1tli,1tlx,2tlx,2tli,3tli,4tli,5tli,6tli,7tli,8tli
[31]
PubMed ID10869357
JournalJ Biol Chem
Year2000
Volume275
Pages31115-20
Authorsde Kreij A, Venema G, van den Burg B
TitleSubstrate specificity in the highly heterogeneous M4 peptidase family is determined by a small subset of amino acids.
[32]
PubMed ID10921773
JournalJ Comput Aided Mol Des
Year2000
Volume14
Pages573-91
AuthorsCosgrove DA, Bayada DM, Johnson AP
TitleA novel method of aligning molecules by local surface shape similarity
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PubMed ID11326120
JournalActa Crystallogr A
Year2001
Volume57
Pages351-8
AuthorsWebster G, Hilgenfeld R
TitleAn evolutionary computational approach to the phase problem in macromolecular X-ray crystallography
[34]
PubMed ID11427942
JournalBiotechnol Bioeng
Year2001
Volume74
Pages406-15
AuthorsMurakami Y, Chiba K, Oda T, Hirata A
TitleNovel kinetic analysis of enzymatic dipeptide synthesis: effect of pH and substrates on thermolysin catalysis
[35]
CommentsX-ray crystallography
PubMed ID11287678
JournalProtein Eng
Year2001
Volume14
Pages47-59
AuthorsEnglish AC, Groom CR, Hubbard RE
TitleExperimental and computational mapping of the binding surface of a crystalline protein
Related PDB1fj3,1fjo,1fjq,1fjt,1fju,1fjv,1fjw
[36]
CommentsX-ray crystallography
PubMed ID12454500
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages2198-200
AuthorsGaucher JF, Selkti M, Prange T, Tomas A
TitleThe 2.2 A resolution structure of thermolysin (TLN) crystallized in the presence of potassium thiocyanate.
Related PDB1gxw
[37]
CommentsX-ray crystallography
PubMed ID12037302
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages1002-7
AuthorsHausrath AC, Matthews BW
TitleThermolysin in the absence of substrate has an open conformation
Related PDB1l3f
[38]
PubMed ID12023041
JournalFEBS Lett
Year2002
Volume519
Pages181-4
AuthorsPedersen NR, Halling PJ, Pedersen LH, Wimmer R, Matthiesen R, Veltman OR
TitleEfficient transesterification of sucrose catalysed by the metalloprotease thermolysin in dimethylsulfoxide
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PubMed ID11996551
JournalJ Am Chem Soc
Year2002
Volume124
Pages5254-5
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TitleMolecular imprinting of enzymes with water-insoluble ligands for nonaqueous biocatalysis
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PubMed ID11859085
JournalJ Biol Chem
Year2002
Volume277
Pages15432-8
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TitleThe effects of modifying the surface charge on the catalytic activity of a thermolysin-like protease.
[41]
PubMed ID11935352
JournalJ Biol Inorg Chem
Year2002
Volume7
Pages284-98
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TitleA theoretical study of the mechanism for peptide hydrolysis by thermolysin.
[42]
PubMed ID11858637
JournalJ Mol Graph Model
Year2002
Volume20
Pages281-95
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TitleConsensus scoring for ligand/protein interactions
[43]
CommentsX-ray crystallography
PubMed ID12832763
JournalActa Crystallogr D Biol Crystallogr
Year2003
Volume59
Pages1200-5
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TitleInteractions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.
Related PDB1os0
[44]
PubMed ID12569506
JournalAngew Chem Int Ed Engl
Year2003
Volume42
Pages421-4
AuthorsKelso MJ, Hoang HN, Oliver W, Sokolenko N, March DR, Appleton TG, Fairlie DP
TitleA cyclic metallopeptide induces alpha helicity in short peptide fragments of thermolysin.
[45]
PubMed ID12735988
JournalBioorg Med Chem
Year2003
Volume11
Pages2421-6
AuthorsKim SJ, Kim DH, Park JD, Woo JR, Jin Y, Ryu SE
TitleOrigin of the stereospecificity in binding hydroxamates of alpha- and beta-phenylalanine methylamide to thermolysin revealed by the X-ray crystallographic study.

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.)

createdupdated
2005-04-012009-03-16


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
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 2010)
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)

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