PDBsum entry 1alw

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Calcium binding PDB id
Protein chains
173 a.a. *
ISA ×2
_CA ×8
Waters ×104
* Residue conservation analysis
PDB id:
Name: Calcium binding
Title: Inhibitor and calcium bound domain vi of porcine calpain
Structure: Calpain. Chain: a, b. Fragment: inhibitor-bound calcium binding domain vi. Synonym: s-camld. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.03Å     R-factor:   0.210     R-free:   0.270
Authors: S.V.L.Narayana,G.Lin
Key ref: G.D.Lin et al. (1997). Crystal structure of calcium bound domain VI of calpain at 1.9 A resolution and its role in enzyme assembly, regulation, and inhibitor binding. Nat Struct Biol, 4, 539-547. PubMed id: 9228946
04-Jun-97     Release date:   10-Jun-98    
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Protein chains
Pfam   ArchSchema ?
P04574  (CPNS1_PIG) -  Calpain small subunit 1
266 a.a.
173 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     calcium ion binding     1 term  


Nat Struct Biol 4:539-547 (1997)
PubMed id: 9228946  
Crystal structure of calcium bound domain VI of calpain at 1.9 A resolution and its role in enzyme assembly, regulation, and inhibitor binding.
G.D.Lin, D.Chattopadhyay, M.Maki, K.K.Wang, M.Carson, L.Jin, P.W.Yuen, E.Takano, M.Hatanaka, L.J.DeLucas, S.V.Narayana.
The three dimensional structure of calcium-bound domain VI of porcine calpain has been determined to 1.9 A resolution. The crystal structure reveals five EF-hands, one more than previously suggested. There are two EF-hand pairs, one pair (EF1-EF2) displays an 'open' conformation and the other (EF3-EF4) a 'closed' conformation. Unusually, a calcium atom is found at the C-terminal end of the calcium binding loop of EF4. With two additional residues in the calcium binding loop, the fifth EF-hand (EF5) is in a 'closed' conformation. EF5 pairs up with the corresponding fifth EF-hand of a non-crystallographically related molecule. Considering the EF5's role in a homodimer formation of domain VI, we suggest a model for the assembly of heterodimeric calpain. The crystal structure of a Ca2+ bound domain VI-inhibitor (PD150606) complex has been refined to 2.1 A resolution. A possible mode for calpain inhibition is discussed.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18673213 B.Govindarajan, J.Laird, R.Sherman, R.G.Salomon, and S.K.Bhattacharya (2008).
Neuroprotection in glaucoma using calpain-1 inhibitors: regional differences in calpain-1 activity in the trabecular meshwork, optic nerve and implications for therapeutics.
  CNS Neurol Disord Drug Targets, 7, 295-304.  
18812568 K.I.Seyb, E.R.Schuman, J.Ni, M.M.Huang, M.L.Michaelis, and M.A.Glicksman (2008).
Identification of small molecule inhibitors of beta-amyloid cytotoxicity through a cell-based high-throughput screening platform.
  J Biomol Screen, 13, 870-878.  
19020622 T.Moldoveanu, K.Gehring, and D.R.Green (2008).
Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains.
  Nature, 456, 404-408.
PDB code: 3df0
17640275 S.Vernarecci, G.Colotti, P.Ornaghi, E.Schiebel, E.Chiancone, and P.Filetici (2007).
The yeast penta-EF protein Pef1p is involved in cation-dependent budding and cell polarization.
  Mol Microbiol, 65, 1122-1138.  
16997142 M.E.Saez, R.Ramirez-Lorca, F.J.Moron, and A.Ruiz (2006).
The therapeutic potential of the calpain family: new aspects.
  Drug Discov Today, 11, 917-923.  
16212623 A.M.Hussain, Q.X.Zhang, and A.G.Murray (2005).
Endothelial cell calpain activity facilitates lymphocyte diapedesis.
  Am J Transplant, 5, 2640-2648.  
16125114 M.Bartoli, and I.Richard (2005).
Calpains in muscle wasting.
  Int J Biochem Cell Biol, 37, 2115-2133.  
14976200 A.Alexa, Z.Bozóky, A.Farkas, P.Tompa, and P.Friedrich (2004).
Contribution of distinct structural elements to activation of calpain by Ca2+ ions.
  J Biol Chem, 279, 20118-20126.  
14570918 K.H.Wu, and P.C.Tai (2004).
Cys32 and His105 are the critical residues for the calcium-dependent cysteine proteolytic activity of CvaB, an ATP-binding cassette transporter.
  J Biol Chem, 279, 901-909.  
15102361 S.Biswas, F.Harris, S.Dennison, J.Singh, and D.A.Phoenix (2004).
Calpains: targets of cataract prevention?
  Trends Mol Med, 10, 78-84.  
14749380 T.Franz, L.Winckler, T.Boehm, and T.N.Dear (2004).
Capn5 is expressed in a subset of T cells and is dispensable for development.
  Mol Cell Biol, 24, 1649-1654.  
14579356 E.K.Leinala, J.S.Arthur, P.Grochulski, P.L.Davies, J.S.Elce, and Z.Jia (2003).
A second binding site revealed by C-terminal truncation of calpain small subunit, a penta-EF-hand protein.
  Proteins, 53, 649-655.
PDB code: 1np8
12711611 M.Mella, G.Colotti, C.Zamparelli, D.Verzili, A.Ilari, and E.Chiancone (2003).
Information transfer in the penta-EF-hand protein sorcin does not operate via the canonical structural/functional pairing. A study with site-specific mutants.
  J Biol Chem, 278, 24921-24928.  
12517342 W.Iwasaki, H.Sasaki, A.Nakamura, K.Kohama, and M.Tanokura (2003).
Metal-free and Ca2+-bound structures of a multidomain EF-hand protein, CBP40, from the lower eukaryote Physarum polycephalum.
  Structure, 11, 75-85.
PDB codes: 1ij5 1ij6
14500891 Z.Mucsi, F.Hudecz, M.Hollósi, P.Tompa, and P.Friedrich (2003).
Binding-induced folding transitions in calpastatin subdomains A and C.
  Protein Sci, 12, 2327-2336.  
12437134 D.Reverter, M.Braun, C.Fernandez-Catalan, S.Strobl, H.Sorimachi, and W.Bode (2002).
Flexibility analysis and structure comparison of two crystal forms of calcium-free human m-calpain.
  Biol Chem, 383, 1415-1422.  
12189137 E.Dainese, R.Minafra, A.Sabatucci, P.Vachette, E.Melloni, and I.Cozzani (2002).
Conformational changes of calpain from human erythrocytes in the presence of Ca2+.
  J Biol Chem, 277, 40296-40301.  
12379807 S.Dewitt, and M.B.Hallett (2002).
Cytosolic free Ca(2+) changes and calpain activation are required for beta integrin-accelerated phagocytosis by human neutrophils.
  J Cell Biol, 159, 181-189.  
11796727 T.Maruoka, Y.Nagasoe, S.Inoue, Y.Mori, J.Goto, M.Ikeda, and H.Iida (2002).
Essential hydrophilic carboxyl-terminal regions including cysteine residues of the yeast stretch-activated calcium-permeable channel Mid1.
  J Biol Chem, 277, 11645-11652.  
11258679 B.G.Díaz, S.Gross, I.Assfalg-Machleidt, D.Pfeiler, N.Gollmitzer, D.Gabrijelcic-Geiger, M.T.Stubbs, H.Fritz, E.A.Auerswald, and W.Machleidt (2001).
Cystatins as calpain inhibitors: engineered chicken cystatin- and stefin B-kininogen domain 2 hybrids support a cystatin-like mode of interaction with the catalytic subunit of mu-calpain.
  Biol Chem, 382, 97.  
11517928 D.Reverter, S.Strobl, C.Fernandez-Catalan, H.Sorimachi, K.Suzuki, and W.Bode (2001).
Structural basis for possible calcium-induced activation mechanisms of calpains.
  Biol Chem, 382, 753-766.  
11525164 J.Jia, S.Tarabykina, C.Hansen, M.Berchtold, and M.Cygler (2001).
Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins.
  Structure, 9, 267-275.
PDB code: 1hqv
11714909 X.Xie, M.D.Dwyer, L.Swenson, M.H.Parker, and M.C.Botfield (2001).
Crystal structure of calcium-free human sorcin: a member of the penta-EF-hand protein family.
  Protein Sci, 10, 2419-2425.
PDB code: 1juo
11516996 Y.Huang, and K.K.Wang (2001).
The calpain family and human disease.
  Trends Mol Med, 7, 355-362.  
11114499 A.Lewit-Bentley, and S.Réty (2000).
EF-hand calcium-binding proteins.
  Curr Opin Struct Biol, 10, 637-643.  
10651630 C.Zamparelli, A.Ilari, D.Verzili, L.Giangiacomo, G.Colotti, S.Pascarella, and E.Chiancone (2000).
Structure-function relationships in sorcin, a member of the penta EF-hand family. Interaction of sorcin fragments with the ryanodine receptor and an Escherichia coli model system.
  Biochemistry, 39, 658-666.  
10830478 H.Kitagaki, S.Tomioka, T.Yoshizawa, H.Sorimachi, T.C.Saido, S.Ishiura, and K.Suzuki (2000).
Autolysis of calpain large subunit inducing irreversible dissociation of stoichiometric heterodimer of calpain.
  Biosci Biotechnol Biochem, 64, 689-695.  
10825211 J.S.Arthur, J.S.Elce, C.Hegadorn, K.Williams, and P.A.Greer (2000).
Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division.
  Mol Cell Biol, 20, 4474-4481.  
  10783162 S.B.Sokol, and P.E.Kuwabara (2000).
Proteolysis in Caenorhabditis elegans sex determination: cleavage of TRA-2A by TRA-3.
  Genes Dev, 14, 901-906.  
10639123 S.Strobl, C.Fernandez-Catalan, M.Braun, R.Huber, H.Masumoto, K.Nakagawa, A.Irie, H.Sorimachi, G.Bourenkow, H.Bartunik, K.Suzuki, and W.Bode (2000).
The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium.
  Proc Natl Acad Sci U S A, 97, 588-592.
PDB codes: 1dkv 1kfu 1kfx
  11152121 T.Berggård, E.Thulin, K.S.Akerfeldt, and S.Linse (2000).
Fragment complementation of calbindin D28k.
  Protein Sci, 9, 2094-2108.  
10591109 K.L.Yap, J.B.Ames, M.B.Swindells, and M.Ikura (1999).
Diversity of conformational states and changes within the EF-hand protein superfamily.
  Proteins, 37, 499-507.  
10545326 M.S.Cates, M.B.Berry, E.L.Ho, Q.Li, J.D.Potter, and G.N.Phillips (1999).
Metal-ion affinity and specificity in EF-hand proteins: coordination geometry and domain plasticity in parvalbumin.
  Structure, 7, 1269-1278.
PDB codes: 1b8c 1b8l 1b8r 1b9a
9562557 D.E.Brodersen, M.Etzerodt, P.Madsen, J.E.Celis, H.C.Thøgersen, J.Nyborg, and M.Kjeldgaard (1998).
EF-hands at atomic resolution: the structure of human psoriasin (S100A7) solved by MAD phasing.
  Structure, 6, 477-489.
PDB code: 1psr
9667926 J.Evenäs, A.Malmendal, and S.Forsén (1998).
  Curr Opin Chem Biol, 2, 293-302.  
9593689 J.J.Chen, Y.Hong, E.Rustamzadeh, J.D.Baleja, and E.J.Androphy (1998).
Identification of an alpha helical motif sufficient for association with papillomavirus E6.
  J Biol Chem, 273, 13537-13544.  
9582380 R.P.Guttmann, and G.V.Johnson (1998).
Oxidative stress inhibits calpain activity in situ.
  J Biol Chem, 273, 13331-13338.  
9642272 Y.Ono, H.Shimada, H.Sorimachi, I.Richard, T.C.Saido, J.S.Beckmann, S.Ishiura, and K.Suzuki (1998).
Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A.
  J Biol Chem, 273, 17073-17078.  
  9385641 S.Linse, E.Thulin, L.K.Gifford, D.Radzewsky, J.Hagan, R.R.Wilk, and K.S.Akerfeldt (1997).
Domain organization of calbindin D28k as determined from the association of six synthetic EF-hand fragments.
  Protein Sci, 6, 2385-2396.  
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.