PDBsum entry 8tln

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Hydrolase(metalloproteinase) PDB id
Protein chain
316 a.a. *
_CA ×4
Waters ×157
* Residue conservation analysis

References listed in PDB file
Key reference
Title Structural comparison suggests that thermolysin and related neutral proteases undergo hinge-Bending motion during catalysis.
Authors D.R.Holland, D.E.Tronrud, H.W.Pley, K.M.Flaherty, W.Stark, J.N.Jansonius, D.B.Mckay, B.W.Matthews.
Ref. Biochemistry, 1992, 31, 11310-11316. [DOI no: 10.1021/bi00161a008]
PubMed id 1445869
Crystal structures are known for three members of the bacterial neutral protease family: thermolysin from Bacillus thermoproteolyticus (TLN), the neutral protease from Bacillus cereus (NEU), and the elastase of Pseudomonas aeruginosa (PAE), both in free and ligand-bound forms. Each enzyme consists of an N-terminal and C-terminal domain with the active site formed at the junction of the two domains. Comparison of the different molecules reveals that the structure within each domain is well conserved, but there are substantial hinge-bending displacements (up to 16 degrees) of one domain relative to the other. These domain motions can be correlated with the presence or absence of bound inhibitor, as was previously observed in the specific example of PAE [Thayer, M.M., Flaherty, K.M., & McKay, D.B. (1991) J. Biol. Chem. 266, 2864-2871]. The binding of inhibitor appears to be associated with a reduction of the domain hinge-bending angle by 6-14 degrees and a closure of the "jaws" of the active site cleft by about 2 A. Crystallographic refinement of the structure of thermolysin suggests that electron density seen in the active site of the enzyme in the original structure determination probably corresponds to a bound dipeptide. Thus, the crystal structure appears to correspond to an enzyme-inhibitor or enzyme-product complex, rather than the free enzyme, as has previously been assumed.
Secondary reference #1
Title Structure of thermolysin refined at 1.6 a resolution.
Authors M.A.Holmes, B.W.Matthews.
Ref. J Mol Biol, 1982, 160, 623-639. [DOI no: 10.1016/0022-2836(82)90319-9]
PubMed id 7175940
Full text Abstract
Figure 3.
FIG. 3. Conformational diagram for the backbone of thermolysin. Residues that are outside the ``allowed'' regions for a hard-sphere model are numbered.
Figure 4.
FIG. 4. Stereo diagram illustrating the apparent thermal motion of t,he thermolysin molecule. Larger circles correspond to residues with greater apparen motion. The radius of each c~wlr l\as obtained 1)~ taking the verage R value for all atoms in that residue, subtracting a constant value of 4.0 AZ (in order to make differences in apparent motion more obvious) and drawing the circle at t,hr SO'?; probabilit? level (Johson, 196.5).
The above figures are reproduced from the cited reference with permission from Elsevier
Secondary reference #2
Title Structure of a mercaptan-Thermolysin complex illustrates mode of inhibition of zinc proteases by substrate-Analogue mercaptans.
Authors A.F.Monzingo, B.W.Matthews.
Ref. Biochemistry, 1982, 21, 3390-3394. [DOI no: 10.1021/bi00257a022]
PubMed id 7052122
Full text Abstract
Secondary reference #3
Title Binding of hydroxamic acid inhibitors to crystalline thermolysin suggests a pentacoordinate zinc intermediate in catalysis.
Authors M.A.Holmes, B.W.Matthews.
Ref. Biochemistry, 1981, 20, 6912-6920. [DOI no: 10.1021/bi00527a026]
PubMed id 7317361
Full text Abstract
Secondary reference #4
Title Binding of the biproduct analog l-Benzylsuccinic acid to thermolysin determined by X-Ray crystallography.
Authors M.C.Bolognesi, B.W.Matthews.
Ref. J Biol Chem, 1979, 254, 634-639.
PubMed id 762086
Secondary reference #5
Title Comparison of the structures of carboxypeptidase a and thermolysin.
Authors W.R.Kester, B.W.Matthews.
Ref. J Biol Chem, 1977, 252, 7704-7710.
PubMed id 914833
Secondary reference #6
Title A crystallographic study of the complex of phosphoramidon with thermolysin. A model for the presumed catalytic transition state and for the binding of extended substances.
Authors L.H.Weaver, W.R.Kester, B.W.Matthews.
Ref. J Mol Biol, 1977, 114, 119-132.
PubMed id 909082
Secondary reference #7
Title Crystallographic study of the binding of dipeptide inhibitors to thermolysin: implications for the mechanism of catalysis.
Authors W.R.Kester, B.W.Matthews.
Ref. Biochemistry, 1977, 16, 2506-2516. [DOI no: 10.1021/bi00630a030]
PubMed id 861218
Full text Abstract
Secondary reference #8
Title Role of calcium in the thermal stability of thermolysin.
Authors F.W.Dahlquist, J.W.Long, W.L.Bigbee.
Ref. Biochemistry, 1976, 15, 1103-1111. [DOI no: 10.1021/bi00650a024]
PubMed id 814920
Full text Abstract
Secondary reference #9
Title Evidence of homologous relationship between thermolysin and neutral protease a of bacillus subtilis.
Authors P.L.Levy, M.K.Pangburn, Y.Burstein, L.H.Ericsson, H.Neurath, K.A.Walsh.
Ref. Proc Natl Acad Sci U S A, 1975, 72, 4341-4345. [DOI no: 10.1073/pnas.72.11.4341]
PubMed id 812093
Full text Abstract
Secondary reference #10
Title The conformation of thermolysin.
Authors B.W.Matthews, L.H.Weaver, W.R.Kester.
Ref. J Biol Chem, 1974, 249, 8030-8044.
PubMed id 4214815
Secondary reference #11
Title Binding of lanthanide ions to thermolysin.
Authors B.W.Matthews, L.H.Weaver.
Ref. Biochemistry, 1974, 13, 1719-1725. [DOI no: 10.1021/bi00705a025]
PubMed id 4831359
Full text Abstract
Secondary reference #12
Title The structure of thermolysin: an electron density map at 2-3 a resolution.
Authors P.M.Colman, J.N.Jansonius, B.W.Matthews.
Ref. J Mol Biol, 1972, 70, 701-724. [DOI no: 10.1016/0022-2836(72)90569-4]
PubMed id 5083153
Full text Abstract
Figure 5.
Fra. 5. Schematic diagram, seen from above, of the optical comparator used to build to thermolyein model after Richards, 1968).
Figure 9.
FIG. 9. (a) Key showing tho position of the major binding sites of Llra heavy BWIUS used to determirw thn phase trnglaa fur L~IC therrnolysin elootron density map. and for the folluwing diEcmnoe maps. The calcum positions LIY dotcnninod from tho throo -dinmtional map BK+ indicated in this Figure by crosses. DA&IA, imnrcury acetic acd. (b) DifYeronce electron density bdween atrontillm-thnrmolynin and native themolysin. Tho mnoutmn of this and the following maps are 2-4 L% (c) DifGrence electron den&y betweau barium-lborxnolyuin au3 uetivo thermolyti. (d) Diffeence obctro density between dysprosium-thermolyain and native thomolysin.
The above figures are reproduced from the cited reference with permission from Elsevier
Secondary reference #13
Title Amino-Acid sequence of thermolysin
Authors K.Titani, M.A.Hermodson, L.H.Ericsson, K.A.Walsh, H.Neurath.
Ref. nature new biol, 1972, 238, 35.
Secondary reference #14
Title Three dimensional structure of thermolysin
Authors B.W.Matthews, J.N.Jansonius, P.M.Colman, B.P.Schoenborn, D.Duporque.
Ref. nature new biol, 1972, 238, 37.
Secondary reference #15
Title Structure of thermolysin
Authors B.W.Matthews, P.M.Colman, J.N.Jansonius, K.Titani, K.A.Walsh, H.Neurath.
Ref. nature new biol, 1972, 238, 41.
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