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PDBsum entry 6tmn

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
6tmn
Jmol
Contents
Protein chain
316 a.a. *
Ligands
0PI
Metals
_ZN
_CA ×4
Waters ×170
* Residue conservation analysis
PDB id:
6tmn
Name: Hydrolase/hydrolase inhibitor
Title: Structures of two thermolysin-inhibitor complexes that diffe single hydrogen bond
Structure: Thermolysin. Chain: e. Engineered: yes
Source: Bacillus thermoproteolyticus. Organism_taxid: 1427
Biol. unit: Tetramer (from PQS)
Resolution:
1.60Å     R-factor:   0.171    
Authors: D.E.Tronrud,H.M.Holden,B.W.Matthews
Key ref: D.E.Tronrud et al. (1987). Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond. Science, 235, 571-574. PubMed id: 3810156 DOI: 10.1126/science.3810156
Date:
29-Jun-87     Release date:   09-Jan-89    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00800  (THER_BACTH) -  Thermolysin
Seq:
Struc:
 
Seq:
Struc:
548 a.a.
316 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.4.24.27  - Thermolysin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Xaa-|-Leu > Xaa-|-Phe.
      Cofactor: Ca(2+); Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     metalloendopeptidase activity     1 term  

 

 
DOI no: 10.1126/science.3810156 Science 235:571-574 (1987)
PubMed id: 3810156  
 
 
Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond.
D.E.Tronrud, H.M.Holden, B.W.Matthews.
 
  ABSTRACT  
 
The mode of binding to thermolysin of the ester analog Cbz-GlyP-(O)-Leu-Leu has been determined by x-ray crystallography and shown to be virtually identical (maximum difference 0.2 angstrom) with the corresponding peptide analog Cbz-GlyP-(NH)-Leu-Leu. The two inhibitors provide a matched pair of enzyme-inhibitor complexes that differ by 4.1 kilocalories per mole in intrinsic binding energy but are essentially identical except for the presence or absence of a specific hydrogen bond.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20038580 A.Yokota, K.Tsumoto, M.Shiroishi, T.Nakanishi, H.Kondo, and I.Kumagai (2010).
Contribution of asparagine residues to the stabilization of a proteinaceous antigen-antibody complex, HyHEL-10-hen egg white lysozyme.
  J Biol Chem, 285, 7686-7696.
PDB codes: 3a67 3a6b 3a6c
21150094 E.Menach, K.Yasukawa, and K.Inouye (2010).
Effects of site-directed mutagenesis of the loop residue of the N-terminal domain Gly117 of thermolysin on its catalytic activity.
  Biosci Biotechnol Biochem, 74, 2457-2462.  
20876133 X.Gao, J.Wang, D.Q.Yu, F.Bian, B.B.Xie, X.L.Chen, B.C.Zhou, L.H.Lai, Z.X.Wang, J.W.Wu, and Y.Z.Zhang (2010).
Structural basis for the autoprocessing of zinc metalloproteases in the thermolysin family.
  Proc Natl Acad Sci U S A, 107, 17569-17574.
PDB codes: 3nqx 3nqy 3nqz
19152630 O.A.Adekoya, and I.Sylte (2009).
The thermolysin family (m4) of enzymes: therapeutic and biotechnological potential.
  Chem Biol Drug Des, 73, 7.  
17516427 E.Proschak, M.Rupp, S.Derksen, and G.Schneider (2008).
Shapelets: possibilities and limitations of shape-based virtual screening.
  J Comput Chem, 29, 108-114.  
15952884 J.M.Ogle, and V.Ramakrishnan (2005).
Structural insights into translational fidelity.
  Annu Rev Biochem, 74, 129-177.  
12832763 M.Selkti, A.Tomas, J.F.Gaucher, T.Prangé, M.C.Fournié-Zaluski, H.Chen, and B.P.Roques (2003).
Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.
  Acta Crystallogr D Biol Crystallogr, 59, 1200-1205.
PDB codes: 1no0 1os0
11559368 A.de Kreij, B.van den Burg, O.R.Veltman, G.Vriend, G.Venema, and V.G.Eijsink (2001).
The effect of changing the hydrophobic S1' subsite of thermolysin-like proteases on substrate specificity.
  Eur J Biochem, 268, 4985-4991.  
10651278 A.C.English, S.H.Done, L.S.Caves, C.R.Groom, and R.E.Hubbard (1999).
Locating interaction sites on proteins: the crystal structure of thermolysin soaked in 2% to 100% isopropanol.
  Proteins, 37, 628-640.
PDB codes: 1tli 1tlx 2tli 2tlx 3tli 4tli 5tli 6tli 7tli 8tli
10200158 B.Hao, W.Gong, P.T.Rajagopalan, Y.Zhou, D.Pei, and M.K.Chan (1999).
Structural basis for the design of antibiotics targeting peptide deformylase.
  Biochemistry, 38, 4712-4719.
PDB codes: 1bsj 1bsk
  10595562 K.S.Makarova, and N.V.Grishin (1999).
Thermolysin and mitochondrial processing peptidase: how far structure-functional convergence goes.
  Protein Sci, 8, 2537-2540.  
9461077 D.Fleury, S.A.Wharton, J.J.Skehel, M.Knossow, and T.Bizebard (1998).
Antigen distortion allows influenza virus to escape neutralization.
  Nat Struct Biol, 5, 119-123.
PDB codes: 2vir 2vis 2vit 2viu
9029508 G.Klebe, and H.J.Böhm (1997).
Energetic and entropic factors determining binding affinity in protein-ligand complexes.
  J Recept Signal Transduct Res, 17, 459-473.  
9020764 W.Lu, M.A.Qasim, M.Laskowski, and S.B.Kent (1997).
Probing intermolecular main chain hydrogen bonding in serine proteinase-protein inhibitor complexes: chemical synthesis of backbone-engineered turkey ovomucoid third domain.
  Biochemistry, 36, 673-679.  
9228942 Z.Wang, H.Luecke, N.Yao, and F.A.Quiocho (1997).
A low energy short hydrogen bond in very high resolution structures of protein receptor--phosphate complexes.
  Nat Struct Biol, 4, 519-522.
PDB codes: 1ixg 1ixh 1ixi
8952503 B.A.Fields, F.A.Goldbaum, W.Dall'Acqua, E.L.Malchiodi, A.Cauerhff, F.P.Schwarz, X.Ysern, R.J.Poljak, and R.A.Mariuzza (1996).
Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.
  Biochemistry, 35, 15494-15503.
PDB codes: 1kip 1kiq 1kir
8756323 F.Grams, V.Dive, A.Yiotakis, I.Yiallouros, S.Vassiliou, R.Zwilling, W.Bode, and W.Stöcker (1996).
Structure of astacin with a transition-state analogue inhibitor.
  Nat Struct Biol, 3, 671-675.
PDB codes: 1qji 1qjj
8807874 G.MacBeath, and D.Hilvert (1996).
Hydrolytic antibodies: variations on a theme.
  Chem Biol, 3, 433-445.  
7561976 C.McMartin, and R.S.Bohacek (1995).
Flexible matching of test ligands to a 3D pharmacophore using a molecular superposition force field: comparison of predicted and experimental conformations of inhibitors of three enzymes.
  J Comput Aided Mol Des, 9, 237-250.  
  7795520 J.Shen, and J.Wendoloski (1995).
Binding of phosphorus-containing inhibitors to thermolysin studied by the Poisson-Boltzmann method.
  Protein Sci, 4, 373-381.  
  8069228 E.E.Hodgkin, I.C.Gillman, and R.J.Gilbert (1994).
Retrospective analysis of a secondary structure prediction: the catalytic domain of matrix metalloproteinases.
  Protein Sci, 3, 984-986.  
8041800 H.Kubinyi (1994).
[The key and the lock. I. The basis of drug action]
  Pharm Unserer Zeit, 23, 158-168.  
7964924 R.L.DesJarlais, and J.S.Dixon (1994).
A shape- and chemistry-based docking method and its use in the design of HIV-1 protease inhibitors.
  J Comput Aided Mol Des, 8, 231-242.  
8229092 G.Vriend, and V.Eijsink (1993).
Prediction and analysis of structure, stability and unfolding of thermolysin-like proteases.
  J Comput Aided Mol Des, 7, 367-396.  
1818336 S.N.Timasheff, J.M.Andreu, and G.C.Na (1991).
Physical and spectroscopic methods for the evaluation of the interactions of antimitotic agents with tubulin.
  Pharmacol Ther, 52, 191-210.  
1854793 W.J.Lennarz, and W.J.Strittmatter (1991).
Cellular functions of metallo-endoproteinases.
  Biochim Biophys Acta, 1071, 149-158.  
2167850 V.Dive, A.Yiotakis, A.Nicolaou, and F.Toma (1990).
Inhibition of Clostridium histolyticum collagenases by phosphonamide peptide inhibitors.
  Eur J Biochem, 191, 685-693.  
3079537 O.G.Berg, and P.H.von Hippel (1988).
Selection of DNA binding sites by regulatory proteins.
  Trends Biochem Sci, 13, 207-211.  
3065358 P.Vibert, and C.Cohen (1988).
Domains, motions and regulation in the myosin head.
  J Muscle Res Cell Motil, 9, 296-305.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.