PDBsum entry 1cms

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Hydrolase(acid proteinase) PDB id
Protein chain
323 a.a. *
Waters ×297
* Residue conservation analysis
PDB id:
Name: Hydrolase(acid proteinase)
Title: The three-dimensional structure of recombinant bovine chymosin at 2.3 angstroms resolution
Structure: Prochymosin a/b precursor. Chain: a. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913
2.30Å     R-factor:   0.165    
Authors: G.L.Gilliland,E.L.Winborne,J.Nachman,A.Wlodawer
Key ref: G.L.Gilliland et al. (1990). The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution. Proteins, 8, 82. PubMed id: 2217166
12-Oct-89     Release date:   15-Jan-90    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00794  (CHYM_BOVIN) -  Chymosin
381 a.a.
323 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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).
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     aspartic-type endopeptidase activity     1 term  


Proteins 8:82 (1990)
PubMed id: 2217166  
The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution.
G.L.Gilliland, E.L.Winborne, J.Nachman, A.Wlodawer.
The crystal structure of recombinant bovine chymosin (EC; renin), which was cloned and expressed in Escherichia coli, has been determined using X-ray data extending to 2.3 A resolution. The crystals of the enzyme used in this study belong to the space group I222 with unit cell dimensions alpha = 72.7 A, b = 80.3 A, and c = 114.8 A. The structure was solved by the molecular replacement method and was refined by a restrained least-squares procedure. The crystallographic R factor is 0.165 and the deviation of bond distances from ideality is 0.020 A. The resulting model includes all 323 amino acid residues, as well as 297 water molecules. The enzyme has an irregular shape with approximate maximum dimensions of 40 x 50 x 65 A. The secondary structure consists primarily of parallel and antiparallel beta-strands with a few short alpha-helices. The enzyme can be subdivided into N- and C-terminal domains which are separated by a deep cleft containing the active aspartate residues Asp-34 and Asp-216. The amino acid residues and waters at the active site form an extensive hydrogen-bonded network which maintains the pseudo 2-fold symmetry of the entire structure. A comparison of recombinant chymosin with other acid proteinases reveals the high degree of structural similarity with other members of this family of proteins as well as the subtle differences which make chymosin unique. In particular, Tyr-77 of the flap region of chymosin does not hydrogen bond to Trp-42 but protrudes out in the P1 pocket forming hydrophobic interactions with Phe-119 and Leu-32. This may have important implications concerning the mechanism of substrate binding and substrate specificity.

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.  
19285084 P.Bhaumik, H.Xiao, C.L.Parr, Y.Kiso, A.Gustchina, R.Y.Yada, and A.Wlodawer (2009).
Crystal structures of the histo-aspartic protease (HAP) from Plasmodium falciparum.
  J Mol Biol, 388, 520-540.
PDB codes: 3fns 3fnt 3fnu
16216580 A.A.Gorfe, and A.Caflisch (2005).
Functional plasticity in the substrate binding site of beta-secretase.
  Structure, 13, 1487-1498.  
15377517 V.P.Denisov, J.L.Schlessman, B.García-Moreno E, and B.Halle (2004).
Stabilization of internal charges in a protein: water penetration or conformational change?
  Biophys J, 87, 3982-3994.
PDB code: 1u9r
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.  
10861927 A.T.Yagnik, A.Lahm, A.Meola, R.M.Roccasecca, B.B.Ercole, A.Nicosia, and A.Tramontano (2000).
A model for the hepatitis C virus envelope glycoprotein E2.
  Proteins, 40, 355-366.  
  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.  
9271500 G.S.Laco, C.Schalk-Hihi, J.Lubkowski, G.Morris, A.Zdanov, A.Olson, J.H.Elder, A.Wlodawer, and A.Gustchina (1997).
Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor.
  Biochemistry, 36, 10696-10708.
PDB codes: 2fiv 3fiv
  8845753 C.Abad-Zapatero, R.Goldman, S.W.Muchmore, C.Hutchins, K.Stewart, J.Navaza, C.D.Payne, and T.L.Ray (1996).
Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents.
  Protein Sci, 5, 640-652.
PDB code: 1zap
8652792 V.Pavone, G.Gaeta, A.Lombardi, F.Nastri, O.Maglio, C.Isernia, and M.Saviano (1996).
Discovering protein secondary structures: classification and description of isolated alpha-turns.
  Biopolymers, 38, 705-721.  
8591036 S.M.Cutfield, E.J.Dodson, B.F.Anderson, P.C.Moody, C.J.Marshall, P.A.Sullivan, and J.F.Cutfield (1995).
The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors.
  Structure, 3, 1261-1271.
PDB code: 1eag
  7756993 A.A.Adzhubei, and M.J.Sternberg (1994).
Conservation of polyproline II helices in homologous proteins: implications for structure prediction by model building.
  Protein Sci, 3, 2395-2410.  
8064334 J.M.Parker, and R.S.Hodges (1994).
HomologyPlot: searching for homology to a family of proteins using a database of unique conserved patterns.
  J Comput Aided Mol Des, 8, 193-210.  
8159679 K.R.Acharya, R.Shapiro, S.C.Allen, J.F.Riordan, and B.L.Vallee (1994).
Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease.
  Proc Natl Acad Sci U S A, 91, 2915-2919.
PDB code: 1ang
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.  
  8467789 P.Metcalf, and M.Fusek (1993).
Two crystal structures for cathepsin D: the lysosomal targeting signal and active site.
  EMBO J, 12, 1293-1302.  
8259000 S.S.Abdel-Meguid (1993).
Inhibitors of aspartyl proteinases.
  Med Res Rev, 13, 731-778.  
1603805 A.Sali, B.Veerapandian, J.B.Cooper, D.S.Moss, T.Hofmann, and T.L.Blundell (1992).
Domain flexibility in aspartic proteinases.
  Proteins, 12, 158-170.  
1594574 J.A.Hartsuck, G.Koelsch, and S.J.Remington (1992).
The high-resolution crystal structure of porcine pepsinogen.
  Proteins, 13, 1.
PDB code: 3psg
1303065 L.B.Areces, M.B.Bonino, M.A.Parry, E.R.Fraile, H.M.Fernández, and O.Cascone (1992).
Purification and characterization of a milk clotting protease from Mucor bacilliformis.
  Appl Biochem Biotechnol, 37, 283-294.  
1528078 M.D.Walkinshaw (1992).
Protein targets for structure-based drug design.
  Med Res Rev, 12, 317-372.  
  1710977 A.Volbeda, A.Lahm, F.Sakiyama, and D.Suck (1991).
Crystal structure of Penicillium citrinum P1 nuclease at 2.8 A resolution.
  EMBO J, 10, 1607-1618.  
1709492 H.Nakamura, K.Katayanagi, K.Morikawa, and M.Ikehara (1991).
Structural models of ribonuclease H domains in reverse transcriptases from retroviruses.
  Nucleic Acids Res, 19, 1817-1823.  
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.