PDBsum entry 1mpp

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Hydrolase(acid proteinase) PDB id
Protein chain
357 a.a. *
Waters ×221
* Residue conservation analysis
PDB id:
Name: Hydrolase(acid proteinase)
Title: X-ray analyses of aspartic proteinases. V. Structure and refinement at 2.0 angstroms resolution of the aspartic proteinase from mucor pusillus
Structure: Pepsin. Chain: a. Engineered: yes
Source: Rhizomucor pusillus. Organism_taxid: 4840
2.00Å     R-factor:   0.162    
Authors: M.Newman,F.Watson,P.Roychowdhury,H.Jones,M.Badasso, A.Cleasby,S.P.Wood,I.J.Tickle,T.L.Blundell
Key ref: M.Newman et al. (1993). X-ray analyses of aspartic proteinases. V. Structure and refinement at 2.0 A resolution of the aspartic proteinase from Mucor pusillus. J Mol Biol, 230, 260-283. PubMed id: 8450540
19-Feb-92     Release date:   31-Oct-93    
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Protein chain
Pfam   ArchSchema ?
P09177  (CARP_RHIPU) -  Mucorpepsin
427 a.a.
357 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Mucorpepsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins, favoring hydrophobic residues at P1 and P1'. Clots milk. Does not accept Lys at P1, and hence does not activate trypsinogen.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     aspartic-type endopeptidase activity     1 term  


J Mol Biol 230:260-283 (1993)
PubMed id: 8450540  
X-ray analyses of aspartic proteinases. V. Structure and refinement at 2.0 A resolution of the aspartic proteinase from Mucor pusillus.
M.Newman, F.Watson, P.Roychowdhury, H.Jones, M.Badasso, A.Cleasby, S.P.Wood, I.J.Tickle, T.L.Blundell.
The structure of mucor pusillus pepsin (EC, the aspartic proteinase from Mucor pusillus, has been refined to a crystallographic R-factor of 16.2% at 2.0 A resolution. The positions of 2638 protein atoms, 221 solvent atoms and a sulphate ion have been determined with an estimated root-mean-square (r.m.s.) error of 0.15 to 0.20 A. In the final model, the r.m.s. deviation from ideality for bond distances is 0.022 A, and for angle distances it is 0.050 A. Comparison of the overall three-dimensional structure with other aspartic proteinases shows that mucor pusillus pepsin is as distant from the other fungal enzymes as it is from those of mammalian origin. Analysis of a rigid body shift of residues 190 to 302 shows that mucor pusillus pepsin displays one of the largest shifts relative to other aspartic proteinases (14.4 degrees relative to endothiapepsin) and that changes have occurred at the interface between the two rigid bodies to accommodate this large shift. A new sequence alignment has been obtained on the basis of the three-dimensional structure, enabling the positions of large insertions to be identified. Analysis of secondary structure shows the beta-sheet to be well conserved whereas alpha-helical elements are more variable. A new alpha-helix hN4 is formed by a six-residue insertion between positions 131 and 132. Most insertions occur in loop regions: -5 to 1 (five residues relative to porcine pepsin): 115 to 116 (six residues); 186 to 187 (four residues); 263 to 264 (seven residues); 278 to 279 (four residues); and 326 to 332 (six residues). The active site residues are highly conserved in mucor pusillus pepsin; r.m.s. difference with rhizopuspepsin is 0.37 A for 25 C alpha atom pairs. However, residue 303, which is generally conserved as an aspartate, is changed to an asparagine in mucor pusillus pepsin, possibly influencing pH optimum. Substantial changes have occurred in the substrate binding cleft in the region of S1 and S3 due to the insertion between 115 and 116 and the rearrangement of loop 9-13. Residue Asn219 necessitates a shift in position of substrate main-chain atoms to maintain hydrogen bonding pattern. Invariant residues Asp11 and Tyr14 have undergone a major change in conformation apparently due to localized changes in molecular structure. Both these residues have been implicated in zymogen stability and activation.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
10974122 R.Maheshwari, G.Bharadwaj, and M.K.Bhat (2000).
Thermophilic fungi: their physiology and enzymes.
  Microbiol Mol Biol Rev, 64, 461-488.  
10089458 J.Yang, and J.W.Quail (1999).
Structure of the Rhizomucor miehei aspartic proteinase complexed with the inhibitor pepstatin A at 2.7 A resolution.
  Acta Crystallogr D Biol Crystallogr, 55, 625-630.
PDB code: 2rmp
10089409 P.D.Adams, N.S.Pannu, R.J.Read, and A.T.Brunger (1999).
Extending the limits of molecular replacement through combined simulated annealing and maximum-likelihood refinement.
  Acta Crystallogr D Biol Crystallogr, 55, 181-190.  
  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
8749853 D.Frishman, and P.Argos (1995).
Knowledge-based protein secondary structure assignment.
  Proteins, 23, 566-579.  
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
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.  
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