spacer
spacer

PDBsum entry 4cms
Go to PDB code: 
protein links
Hydrolase (acid proteinase) PDB id
4cms

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
320 a.a. *
Waters ×131
* Residue conservation analysis
PDB id:
4cms
Name: Hydrolase (acid proteinase)
Title: X-ray analyses of aspartic proteinases iv. Structure and refinement at 2.2 angstroms resolution of bovine chymosin
Structure: Chymosin b. Chain: a. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913
Resolution:
2.20Å     R-factor:   0.158    
Authors: M.Newman,C.Frazao,G.Khan,I.J.Tickle,T.L.Blundell,M.Safro,N.Andreeva, A.Zdanov
Key ref: M.Newman et al. (1991). X-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2 A resolution of bovine chymosin. J Mol Biol, 221, 1295-1309. PubMed id: 1942052
Date:
01-Nov-91     Release date:   07-Nov-91    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00794  (CHYM_BOVIN) -  Chymosin from Bos taurus
Seq:
Struc: 		381 a.a.
320 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.23.4  - chymosin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Broad specificity similar to that of pepsin A. Clots milk by cleavage of a single bond in casein (kappa chain).

 

 
J Mol Biol 221:1295-1309 (1991)
PubMed id: 1942052  
 
 
X-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2 A resolution of bovine chymosin.
M.Newman, M.Safro, C.Frazao, G.Khan, A.Zdanov, I.J.Tickle, T.L.Blundell, N.Andreeva.
 
  ABSTRACT  
 
The structure of calf chymosin (EC 3.4.23.3), the aspartic proteinase from the gastric mucosa, was solved using the technique of molecular replacement. We describe the use of different search models based on distantly related fungal aspartic proteinases and investigate the effect of using only structurally conserved regions. The structure has been refined to a crystallographic R-factor of 17% at 2.2 A resolution with an estimated co-ordinate error of 0.21 A. In all, 136 water molecules have been located of which eight are internal. The structure of chymosin resembles that of pepsin and other aspartic proteinases. However, there is a considerable rearrangement of the active-site "flap" and, in particular, Tyr75 (pepsin numbering), which forms part of the specificity pockets S1 and S1'. This is probably a consequence of crystal packing. Electrostatic interactions on the edge of the substrate binding cleft appear to account for the restricted proteolysis of the natural substrate kappa-casein by chymosin. The local environment of invariant residues is examined, showing that structural constraints and side-chain hydrogen bonding can play an important role in the conservation of particular amino acids.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20524840 A.Kumar, S.Grover, J.Sharma, and V.K.Batish (2010).
Chymosin and other milk coagulants: sources and biotechnological interventions.
  Crit Rev Biotechnol, 30, 243-258.  
19819898 H.Kageyama, H.Ueda, T.Tezuka, A.Ogasawara, Y.Narita, T.Kageyama, and M.Ichinose (2010).
Differences in the P1' substrate specificities of pepsin A and chymosin.
  J Biochem, 147, 167-174.  
17447722 C.L.Parr, R.A.Keates, B.C.Bryksa, M.Ogawa, and R.Y.Yada (2007).
The structure and function of Saccharomyces cerevisiae proteinase A.
  Yeast, 24, 467-480.  
16216580 A.A.Gorfe, and A.Caflisch (2005).
Functional plasticity in the substrate binding site of beta-secretase.
  Structure, 13, 1487-1498.  
15039581 M.O.Badasso, V.Dhanaraj, S.P.Wood, J.B.Cooper, and T.L.Blundell (2004).
Crystallization and X-ray analysis of the Y75N mutant of Mucor pusillus pepsin complexed with inhibitor.
  Acta Crystallogr D Biol Crystallogr, 60, 770-772.  
11714911 N.S.Andreeva, and L.D.Rumsh (2001).
Analysis of crystal structures of aspartic proteinases: on the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes.
  Protein Sci, 10, 2439-2450.  
11418762 S.W.Cho, N.Kim, M.U.Choi, and W.Shin (2001).
Structure of aspergillopepsin I from Aspergillus phoenicis: variations of the S1'-S2 subsite in aspartic proteinases.
  Acta Crystallogr D Biol Crystallogr, 57, 948-956.
PDB code: 1ibq
  11106168 C.A.Galea, B.P.Dalrymple, R.Kuypers, and R.Blakeley (2000).
Modification of the substrate specificity of porcine pepsin for the enzymatic production of bovine hide gelatin.
  Protein Sci, 9, 1947-1959.  
11015192 H.Chen, G.Zhang, Y.Zhang, Y.Dong, and K.Yang (2000).
Functional implications of disulfide bond, Cys206-Cys210, in recombinant prochymosin (chymosin).
  Biochemistry, 39, 12140-12148.  
10488111 C.Frazão, I.Bento, J.Costa, C.M.Soares, P.Veríssimo, C.Faro, E.Pires, J.Cooper, and M.A.Carrondo (1999).
Crystal structure of cardosin A, a glycosylated and Arg-Gly-Asp-containing aspartic proteinase from the flowers of Cynara cardunculus L.
  J Biol Chem, 274, 27694-27701.
PDB code: 1b5f
10081963 J.A.Cuff, and G.J.Barton (1999).
Evaluation and improvement of multiple sequence methods for protein secondary structure prediction.
  Proteins, 34, 508-519.  
9628859 M.A.Schumacher, D.Carter, D.M.Scott, D.S.Roos, B.Ullman, and R.G.Brennan (1998).
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding.
  EMBO J, 17, 3219-3232.
PDB codes: 1bd3 1bd4 1upf 1upu
9761815 S.Karlsen, E.Hough, and R.L.Olsen (1998).
Structure and proposed amino-acid sequence of a pepsin from atlantic cod (Gadus morhua).
  Acta Crystallogr D Biol Crystallogr, 54, 32-46.
PDB code: 1am5
9228062 T.Shintani, K.Nomura, and E.Ichishima (1997).
Engineering of porcine pepsin. Alteration of S1 substrate specificity of pepsin to those of fungal aspartic proteinases by site-directed mutagenesis.
  J Biol Chem, 272, 18855-18861.  
8913621 G.Iliadis, B.Brzezinski, and G.Zundel (1996).
Aspartic proteinases: Fourier transform infrared spectroscopic studies of a model of the active side.
  Biophys J, 71, 2840-2847.  
8035212 S.D.Rufino, and T.L.Blundell (1994).
Structure-based identification and clustering of protein families and superfamilies.
  J Comput Aided Mol Des, 8, 5.  
  8251933 A.W.Chan, E.G.Hutchinson, D.Harris, and J.M.Thornton (1993).
Identification, classification, and analysis of beta-bulges in proteins.
  Protein Sci, 2, 1574-1590.  
  8443603 P.E.Scarborough, K.Guruprasad, C.Topham, G.R.Richo, G.E.Conner, T.L.Blundell, and B.M.Dunn (1993).
Exploration of subsite binding specificity of human cathepsin D through kinetics and rule-based molecular modeling.
  Protein Sci, 2, 264-276.  
8259000 S.S.Abdel-Meguid (1993).
Inhibitors of aspartyl proteinases.
  Med Res Rev, 13, 731-778.  
8404890 T.Kageyama (1993).
Rabbit procathepsin E and cathepsin E. Nucleotide sequence of cDNA, hydrolytic specificity for biologically active peptides and gene expression during development.
  Eur J Biochem, 216, 717-728.  
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 code is shown on the right.

 

spacer
spacer