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PDBsum entry 1stf

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protein Protein-protein interface(s) links
Hydrolase(sulfhydryl proteinase) PDB id
1stf
Jmol
Contents
Protein chains
212 a.a. *
98 a.a. *
Waters ×142
* Residue conservation analysis
PDB id:
1stf
Name: Hydrolase(sulfhydryl proteinase)
Title: The refined 2.4 angstroms x-ray crystal structure of recombinant human stefin b in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction
Structure: Papain. Chain: e. Engineered: yes. Stefin b (cystatin b). Chain: i. Engineered: yes
Source: Carica papaya. Papaya. Organism_taxid: 3649. Organ: fruit. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Dimer (from PQS)
Resolution:
2.37Å     R-factor:   0.190    
Authors: M.T.Stubbs,B.Laber,W.Bode
Key ref: M.T.Stubbs et al. (1990). The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction. EMBO J, 9, 1939-1947. PubMed id: 2347312
Date:
21-Apr-93     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00784  (PAPA1_CARPA) -  Papain
Seq:
Struc:
345 a.a.
212 a.a.*
Protein chain
Pfam   ArchSchema ?
P04080  (CYTB_HUMAN) -  Cystatin-B
Seq:
Struc:
98 a.a.
98 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain E: E.C.3.4.22.2  - Papain.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins with broad specificity for peptide bonds, with preference for a residue bearing a large hydrophobic sidechain at the P2 position. Does not accept Val at P1'.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   6 terms 
  Biological process     adult locomotory behavior   6 terms 
  Biochemical function     peptidase inhibitor activity     6 terms  

 

 
EMBO J 9:1939-1947 (1990)
PubMed id: 2347312  
 
 
The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction.
M.T.Stubbs, B.Laber, W.Bode, R.Huber, R.Jerala, B.Lenarcic, V.Turk.
 
  ABSTRACT  
 
A stoichiometric complex of human stefin B and carboxymethylated papain has been crystallized in a trigonal crystal form. Data to 2.37 A resolution were collected using the area detector diffractometer FAST. The crystal structure of the complex has been solved by Patterson search techniques using papain as search model. Starting from the structure of chicken cystatin, the stefin structure was elucidated through cycles of model building and crystallographic refinement. The current crystallographic R factor is 0.19. Like cystatin, the stefin molecule consists of a five stranded beta-sheet wrapped around a five turn alpha-helix, but with an additional carboxy terminal strand running along the convex side of the sheet. Topological equivalence of stefin and cystatin reveal the previous sequence alignment to be incorrect in part, through deletion of the intermediate helix. The conserved residues form a tripartite wedge, which slots into the papain active site as proposed through consideration of the tertiary structures of the individual components (Bode et al., 1988). The main interactions are provided by the amino terminal 'trunk' (occupying the 'unprimed' subsites of the enzyme), and by the first hairpin loop, containing the highly conserved QVVAG sequence, with minor contributions from the second hairpin loop. The carboxyl terminus of stefin provides an additional interaction region with respect to cystatin. The interaction is dominated by hydrophobic contacts. Inhibition by the cysteine proteinase inhibitors is fundamentally different to that observed for the serine proteinase inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21354219 J.M.Kang, K.H.Lee, W.M.Sohn, and B.K.Na (2011).
Identification and functional characterization of CsStefin-1, a cysteine protease inhibitor of Clonorchis sinensis.
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20567901 L.Carrillo, M.Martinez, F.Alvarez-Alfageme, P.Castañera, G.Smagghe, I.Diaz, and F.Ortego (2011).
A barley cysteine-proteinase inhibitor reduces the performance of two aphid species in artificial diets and transgenic Arabidopsis plants.
  Transgenic Res, 20, 305-319.  
21082183 L.Carrillo, M.Martinez, K.Ramessar, I.Cambra, P.Castañera, F.Ortego, and I.Díaz (2011).
Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases.
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21429631 L.Rizzi, S.Sundararaman, K.Cendic, N.Vaiana, R.Korde, D.Sinha, A.Mohmmed, P.Malhotra, and S.Romeo (2011).
Design and synthesis of protein-protein interaction mimics as Plasmodium falciparum cysteine protease, falcipain-2 inhibitors.
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20545626 J.Salát, G.C.Paesen, P.Rezácová, M.Kotsyfakis, Z.Kovárová, M.Sanda, J.Majtán, L.Grunclová, H.Horká, J.F.Andersen, J.Brynda, M.Horn, M.A.Nunn, P.Kopácek, J.Kopecký, and M.Mares (2010).
Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.
  Biochem J, 429, 103-112.
PDB code: 3l0r
19955183 K.Skerget, A.Taler-Vercic, A.Bavdek, V.Hodnik, S.Ceru, M.Tusek-Znidaric, T.Kumm, D.Pitsi, M.Pompe-Novak, P.Palumaa, S.Soriano, N.Kopitar-Jerala, V.Turk, G.Anderluh, and E.Zerovnik (2010).
Interaction between oligomers of stefin B and amyloid-beta in vitro and in cells.
  J Biol Chem, 285, 3201-3210.  
20545851 M.Kotsyfakis, H.Horka, J.Salat, and J.F.Andersen (2010).
The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model.
  Mol Microbiol, 77, 456-470.
PDB codes: 3lh4 3li7 3mwz
19597935 M.Priyadarshini, and B.Bano (2010).
Cystatin like thiol proteinase inhibitor from pancreas of Capra hircus: purification and detailed biochemical characterization.
  Amino Acids, 38, 1001-1010.  
19846555 M.Renko, J.Sabotic, M.Mihelic, J.Brzin, J.Kos, and D.Turk (2010).
Versatile loops in mycocypins inhibit three protease families.
  J Biol Chem, 285, 308-316.
PDB codes: 3h6q 3h6r 3h6s
20860624 M.Renko, U.Požgan, D.Majera, and D.Turk (2010).
Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft.
  FEBS J, 277, 4338-4345.
PDB code: 3k9m
20920298 N.F.Valadares, M.Dellamano, A.Soares-Costa, F.Henrique-Silva, and R.C.Garratt (2010).
Molecular determinants of improved cathepsin B inhibition by new cystatins obtained by DNA shuffling.
  BMC Struct Biol, 10, 30.  
20175878 R.Kolodziejczyk, K.Michalska, A.Hernandez-Santoyo, M.Wahlbom, A.Grubb, and M.Jaskolski (2010).
Crystal structure of human cystatin C stabilized against amyloid formation.
  FEBS J, 277, 1726-1737.
PDB code: 3gax
20078424 S.Ceru, R.Layfield, T.Zavasnik-Bergant, U.Repnik, N.Kopitar-Jerala, V.Turk, and E.Zerovnik (2010).
Intracellular aggregation of human stefin B: confocal and electron microscopy study.
  Biol Cell, 102, 319-334.  
20075068 S.Ceru, S.Konjar, K.Maher, U.Repnik, I.Krizaj, M.Bencina, M.Renko, A.Nepveu, E.Zerovnik, B.Turk, and N.Kopitar-Jerala (2010).
Stefin B interacts with histones and cathepsin L in the nucleus.
  J Biol Chem, 285, 10078-10086.  
20179045 T.Hoffmann, L.K.Stadler, M.Busby, Q.Song, A.T.Buxton, S.D.Wagner, J.J.Davis, and P.Ko Ferrigno (2010).
Structure-function studies of an engineered scaffold protein derived from stefin A. I: Development of the SQM variant.
  Protein Eng Des Sel, 23, 403-413.  
19919722 D.Kordis, and V.Turk (2009).
Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes.
  BMC Evol Biol, 9, 266.  
19143838 I.Redzynia, A.Ljunggren, A.Bujacz, M.Abrahamson, M.Jaskolski, and G.Bujacz (2009).
Crystal structure of the parasite inhibitor chagasin in complex with papain allows identification of structural requirements for broad reactivity and specificity determinants for target proteases.
  FEBS J, 276, 793-806.
PDB code: 3e1z
19192250 J.D.Colbert, A.Plechanovová, and C.Watts (2009).
Glycosylation directs targeting and activation of cystatin f from intracellular and extracellular sources.
  Traffic, 10, 425-437.  
19104918 K.Doi-Kawano, E.Nishimoto, Y.Kouzuma, D.Takahashi, S.Yamashita, and M.Kimura (2009).
Steady-state and time-resolved fluorescence spectroscopic studies on interaction of the N-terminal region with the hairpin loop of the phytocystatin Scb.
  J Fluoresc, 19, 631-639.  
19137579 S.Rodziewicz-Motowidło, J.Iwaszkiewicz, R.Sosnowska, P.Czaplewska, E.Sobolewski, A.Szymańska, K.Stachowiak, and A.Liwo (2009).
The role of the Val57 amino-acid residue in the hinge loop of the human cystatin C. Conformational studies of the beta2-L1-beta3 segments of wild-type human cystatin C and its mutants.
  Biopolymers, 91, 373-383.  
18783611 C.Serbielle, S.Chowdhury, S.Pichon, S.Dupas, J.Lesobre, E.O.Purisima, J.M.Drezen, and E.Huguet (2008).
Viral cystatin evolution and three-dimensional structure modelling: a case of directional selection acting on a viral protein involved in a host-parasitoid interaction.
  BMC Biol, 6, 38.  
18256700 G.Hamilton, J.D.Colbert, A.W.Schuettelkopf, and C.Watts (2008).
Cystatin F is a cathepsin C-directed protease inhibitor regulated by proteolysis.
  EMBO J, 27, 499-508.  
18787201 J.Davis, J.Wang, J.E.Tropea, D.Zhang, Z.Dauter, D.S.Waugh, and A.Wlodawer (2008).
Novel fold of VirA, a type III secretion system effector protein from Shigella flexneri.
  Protein Sci, 17, 2167-2173.
PDB code: 3ee1
18616807 M.Martinez, and I.Diaz (2008).
The origin and evolution of plant cystatins and their target cysteine proteinases indicate a complex functional relationship.
  BMC Evol Biol, 8, 198.  
18632274 S.Zhu (2008).
Did cathelicidins, a family of multifunctional host-defense peptides, arise from a cysteine protease inhibitor?
  Trends Microbiol, 16, 353-360.  
18028412 T.Joensuu, A.E.Lehesjoki, and O.Kopra (2008).
Molecular background of EPM1-Unverricht-Lundborg disease.
  Epilepsia, 49, 557-563.  
17886319 D.J.van Zoelen, M.R.Egmond, R.J.Pieters, and R.M.Liskamp (2007).
Synthesis and evaluation of TAC-based inhibitors of papain as mimics of cystatin B.
  Chembiochem, 8, 1950-1956.  
17976004 M.Mihelic, and D.Turk (2007).
Two decades of thyroglobulin type-1 domain research.
  Biol Chem, 388, 1123-1130.  
17502099 S.X.Wang, K.C.Pandey, J.Scharfstein, J.Whisstock, R.K.Huang, J.Jacobelli, R.J.Fletterick, P.J.Rosenthal, M.Abrahamson, L.S.Brinen, A.Rossi, A.Sali, and J.H.McKerrow (2007).
The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family.
  Structure, 15, 535-543.
PDB code: 2oul
17003839 T.Joensuu, M.Kuronen, K.Alakurtti, S.Tegelberg, P.Hakala, A.Aalto, L.Huopaniemi, N.Aula, R.Michellucci, K.Eriksson, and A.E.Lehesjoki (2007).
Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients.
  Eur J Hum Genet, 15, 185-193.  
17681235 T.Miyaji, Y.Kouzuma, J.Yaguchi, R.Matsumoto, M.R.Kanost, K.J.Kramer, and M.Yonekura (2007).
Purification of a cysteine protease inhibitor from larval hemolymph of the tobacco hornworm (Manduca sexta) and functional expression of the recombinant protein.
  Insect Biochem Mol Biol, 37, 960-968.  
16965553 A.Kiggundu, M.C.Goulet, C.Goulet, J.F.Dubuc, D.Rivard, M.Benchabane, G.Pépin, C.van der Vyver, K.Kunert, and D.Michaud (2006).
Modulating the proteinase inhibitory profile of a plant cystatin by single mutations at positively selected amino acid sites.
  Plant J, 48, 403-413.  
16601115 A.W.Schüttelkopf, G.Hamilton, C.Watts, and D.M.van Aalten (2006).
Structural basis of reduction-dependent activation of human cystatin F.
  J Biol Chem, 281, 16570-16575.
PDB code: 2ch9
16407198 B.O.Smith, N.C.Picken, G.D.Westrop, K.Bromek, J.C.Mottram, and G.H.Coombs (2006).
The structure of Leishmania mexicana ICP provides evidence for convergent evolution of cysteine peptidase inhibitors.
  J Biol Chem, 281, 5821-5828.
PDB code: 2c34
16955069 B.Turk (2006).
Targeting proteases: successes, failures and future prospects.
  Nat Rev Drug Discov, 5, 785-799.  
16939620 E.Zerovnik, K.Skerget, M.Tusek-Znidaric, C.Loeschner, M.W.Brazier, and D.R.Brown (2006).
High affinity copper binding by stefin B (cystatin B) and its role in the inhibition of amyloid fibrillation.
  FEBS J, 273, 4250-4263.  
16470583 J.M.Aguiar, O.L.Franco, D.J.Rigden, C.Bloch, A.C.Monteiro, V.M.Flores, T.Jacinto, J.Xavier-Filho, A.E.Oliveira, M.F.Grossi-de-Sá, and K.V.Fernandes (2006).
Molecular modeling and inhibitory activity of cowpea cystatin against bean bruchid pests.
  Proteins, 63, 662-670.  
16342276 M.Kenig, S.Jenko-Kokalj, M.Tusek-Znidaric, M.Pompe-Novak, G.Guncar, D.Turk, J.P.Waltho, R.A.Staniforth, F.Avbelj, and E.Zerovnik (2006).
Folding and amyloid-fibril formation for a series of human stefins' chimeras: any correlation?
  Proteins, 62, 918-927.  
17016021 S.Akashi (2006).
[Structural and functional characterization of biological macromolecules by mass spectrometry]
  Yakugaku Zasshi, 126, 915-929.  
16864794 S.X.Wang, K.C.Pandey, J.R.Somoza, P.S.Sijwali, T.Kortemme, L.S.Brinen, R.J.Fletterick, P.J.Rosenthal, and J.H.McKerrow (2006).
Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease.
  Proc Natl Acad Sci U S A, 103, 11503-11508.
PDB code: 1yvb
15698574 A.Aagaard, P.Listwan, N.Cowieson, T.Huber, T.Ravasi, C.A.Wells, J.U.Flanagan, S.Kellie, D.A.Hume, B.Kobe, and J.L.Martin (2005).
An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1.
  Structure, 13, 309-317.
PDB code: 1wnh
15489503 D.A.Breustedt, I.P.Korndörfer, B.Redl, and A.Skerra (2005).
The 1.8-A crystal structure of human tear lipocalin reveals an extended branched cavity with capacity for multiple ligands.
  J Biol Chem, 280, 484-493.
PDB code: 1xki
15738388 I.Pallarès, R.Bonet, R.García-Castellanos, S.Ventura, F.X.Avilés, J.Vendrell, and F.X.Gomis-Rüth (2005).
Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin.
  Proc Natl Acad Sci U S A, 102, 3978-3983.
PDB codes: 2bk7 2bo9
15775973 J.Otlewski, F.Jelen, M.Zakrzewska, and A.Oleksy (2005).
The many faces of protease-protein inhibitor interaction.
  EMBO J, 24, 1303-1310.  
15728581 M.Alvarez-Fernandez, Y.H.Liang, M.Abrahamson, and X.D.Su (2005).
Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.
  J Biol Chem, 280, 18221-18228.
PDB codes: 1rn7 1roa
15904486 S.Nakai, E.C.Li-Chan, and J.Dou (2005).
Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins.
  BMC Biochem, 6, 9.  
16003951 S.P.Baba, S.Zehra, and B.Bano (2005).
Purification and characterization of kininogens from sheep plasma.
  Protein J, 24, 95.  
16155205 S.Rabzelj, V.Turk, and E.Zerovnik (2005).
In vitro study of stability and amyloid-fibril formation of two mutants of human stefin B (cystatin B) occurring in patients with EPM1.
  Protein Sci, 14, 2713-2722.  
16045611 T.F.Kagawa, P.W.O'toole, and J.C.Cooney (2005).
SpeB-Spi: a novel protease-inhibitor pair from Streptococcus pyogenes.
  Mol Microbiol, 57, 650-666.  
14747998 B.Japelj, J.P.Waltho, and R.Jerala (2004).
Comparison of backbone dynamics of monomeric and domain-swapped stefin A.
  Proteins, 54, 500-512.  
14691222 M.Kenig, S.Berbić, A.Krijestorac, L.Kroon-Zitko, M.Tusek, M.Pompe-Novak, and E.Zerovnik (2004).
Differences in aggregation properties of three site-specific mutants of recombinant human stefin B.
  Protein Sci, 13, 63-70.  
15048832 S.Jenko, M.Skarabot, M.Kenig, G.Guncar, I.Musevic, D.Turk, and E.Zerovnik (2004).
Different propensity to form amyloid fibrils by two homologous proteins-Human stefins A and B: searching for an explanation.
  Proteins, 55, 417-425.  
12853462 A.E.Lehesjoki (2003).
Molecular background of progressive myoclonus epilepsy.
  EMBO J, 22, 3473-3478.  
12787025 B.Belenghi, F.Acconcia, M.Trovato, M.Perazzolli, A.Bocedi, F.Polticelli, P.Ascenzi, and M.Delledonne (2003).
AtCYS1, a cystatin from Arabidopsis thaliana, suppresses hypersensitive cell death.
  Eur J Biochem, 270, 2593-2604.  
12887049 B.Turk, H.Fritz, and V.Turk (2003).
Vito Turk--30 years of research on cysteine proteases and their inhibitors.
  Biol Chem, 384, 833-836.  
12554931 D.Turk, and G.Guncar (2003).
Lysosomal cysteine proteases (cathepsins): promising drug targets.
  Acta Crystallogr D Biol Crystallogr, 59, 203-213.  
12931008 J.R.Bradford, and D.R.Westhead (2003).
Asymmetric mutation rates at enzyme-inhibitor interfaces: implications for the protein-protein docking problem.
  Protein Sci, 12, 2099-2103.  
12874290 R.Filipek, M.Rzychon, A.Oleksy, M.Gruca, A.Dubin, J.Potempa, and M.Bochtler (2003).
The Staphostatin-staphopain complex: a forward binding inhibitor in complex with its target cysteine protease.
  J Biol Chem, 278, 40959-40966.
PDB code: 1pxv
11790528 A.M.Lennon-Duménil, A.H.Bakker, P.Wolf-Bryant, H.L.Ploegh, and C.Lagaudrière-Gesbert (2002).
A closer look at proteolysis and MHC-class-II-restricted antigen presentation.
  Curr Opin Immunol, 14, 15-21.  
12423365 A.Pavlova, and I.Björk (2002).
The role of the second binding loop of the cysteine protease inhibitor, cystatin A (stefin A), in stabilizing complexes with target proteases is exerted predominantly by Leu73.
  Eur J Biochem, 269, 5649-5658.  
12142451 D.J.Rigden, V.V.Mosolov, and M.Y.Galperin (2002).
Sequence conservation in the chagasin family suggests a common trend in cysteine proteinase binding by unrelated protein inhibitors.
  Protein Sci, 11, 1971-1977.  
11852247 H.R.Stennicke, C.A.Ryan, and G.S.Salvesen (2002).
Reprieval from execution: the molecular basis of caspase inhibition.
  Trends Biochem Sci, 27, 94.  
11771999 J.F.Sanchez, F.Wojcik, Y.S.Yang, M.P.Strub, J.M.Strub, A.Van Dorsselaer, M.Martin, R.Lehrer, T.Ganz, A.Chavanieu, B.Calas, and A.Aumelas (2002).
Overexpression and structural study of the cathelicidin motif of the protegrin-3 precursor.
  Biochemistry, 41, 21-30.  
12065604 J.Hong, K.Yoshida, and M.R.Rosner (2002).
Characterization of a cysteine proteinase inhibitor induced during neuronal cell differentiation.
  J Neurochem, 81, 922-934.  
11514663 E.Pol, and I.Björk (2001).
Role of the single cysteine residue, Cys 3, of human and bovine cystatin B (stefin B) in the inhibition of cysteine proteinases.
  Protein Sci, 10, 1729-1738.  
11576423 H.Koiwa, M.P.D'Urzo, I.Assfalg-Machleidt, K.Zhu-Salzman, R.E.Shade, H.An, L.L.Murdock, W.Machleidt, R.A.Bressan, and P.M.Hasegawa (2001).
Phage display selection of hairpin loop soyacystatin variants that mediate high affinity inhibition of a cysteine proteinase.
  Plant J, 27, 383-391.  
11529899 K.Ichikawa, L.D.Vailes, A.Pomés, and M.D.Chapman (2001).
Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor.
  Clin Exp Allergy, 31, 1279-1286.  
11299325 M.Calero, M.Pawlik, C.Soto, E.M.Castaño, E.M.Sigurdsson, A.Kumar, G.Gallo, B.Frangione, and E.Levy (2001).
Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type.
  J Neurochem, 77, 628-637.  
11170205 M.Kenig, R.Jerala, L.Kroon-Zitko, V.Turk, and E.Zerovnik (2001).
Major differences in stability and dimerization properties of two chimeric mutants of human stefins.
  Proteins, 42, 512-522.  
11532941 R.A.Staniforth, S.Giannini, L.D.Higgins, M.J.Conroy, A.M.Hounslow, R.Jerala, C.J.Craven, and J.P.Waltho (2001).
Three-dimensional domain swapping in the folded and molten-globule states of cystatins, an amyloid-forming structural superfamily.
  EMBO J, 20, 4774-4781.
PDB code: 1n9j
11257232 S.J.Riedl, M.Renatus, R.Schwarzenbacher, Q.Zhou, C.Sun, S.W.Fesik, R.C.Liddington, and G.S.Salvesen (2001).
Structural basis for the inhibition of caspase-3 by XIAP.
  Cell, 104, 791-800.
PDB code: 1i3o
11532926 V.Turk, B.Turk, and D.Turk (2001).
Lysosomal cysteine proteases: facts and opportunities.
  EMBO J, 20, 4629-4633.  
11388484 Y.Kouzuma, K.Tsukigata, H.Inanaga, K.Doi-Kawano, N.Yamasaki, and M.Kimura (2001).
Molecular cloning and functional expression of cDNA encoding the cysteine proteinase inhibitor Sca from sunflower seeds.
  Biosci Biotechnol Biochem, 65, 969-972.  
11123903 C.J.Craven, N.J.Baxter, E.H.Murray, N.J.Hill, J.R.Martin, K.Ylinenjärvi, I.Björk, J.P.Waltho, and I.A.Murray (2000).
Wild-type and met-65-->Leu variants of human cystatin A are functionally and structurally identical.
  Biochemistry, 39, 15783-15790.  
10745011 G.Guncar, I.Klemencic, B.Turk, V.Turk, A.Karaoglanovic-Carmona, L.Juliano, and D.Turk (2000).
Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease.
  Structure, 8, 305-313.
PDB code: 1ef7
11101290 K.Nagata, N.Kudo, K.Abe, S.Arai, and M.Tanokura (2000).
Three-dimensional solution structure of oryzacystatin-I, a cysteine proteinase inhibitor of the rice, Oryza sativa L. japonica.
  Biochemistry, 39, 14753-14760.
PDB code: 1eqk
  11206071 S.Akashi, and K.Takio (2000).
Characterization of the interface structure of enzyme-inhibitor complex by using hydrogen-deuterium exchange and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
  Protein Sci, 9, 2497-2505.  
  11152132 S.Estrada, S.T.Olson, E.Raub-Segall, and I.Björk (2000).
The N-terminal region of cystatin A (stefin A) binds to papain subsequent to the two hairpin loops of the inhibitor. Demonstration of two-step binding by rapid-kinetic studies of cystatin A labeled at the N-terminus with a fluorescent reporter group.
  Protein Sci, 9, 2218-2224.  
11154074 T.Kato, T.Imatani, T.Miura, K.Minaguchi, E.Saitoh, and K.Okuda (2000).
Cytokine-inducing activity of family 2 cystatins.
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10350606 C.Czaplewski, Z.Grzonka, M.Jaskólski, F.Kasprzykowski, M.Kozak, E.Politowska, and J.Ciarkowski (1999).
Binding modes of a new epoxysuccinyl-peptide inhibitor of cysteine proteases. Where and how do cysteine proteases express their selectivity?
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10398367 E.Zerovnik, R.Virden, R.Jerala, L.Kroon-Zitko, V.Turk, and J.P.Waltho (1999).
Differences in the effects of TFE on the folding pathways of human stefins A and B.
  Proteins, 36, 205-216.  
10022822 G.Guncar, G.Pungercic, I.Klemencic, V.Turk, and D.Turk (1999).
Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S.
  EMBO J, 18, 793-803.
PDB code: 1icf
10611646 J.D.Tyndall, and D.P.Fairlie (1999).
Conformational homogeneity in molecular recognition by proteolytic enzymes.
  J Mol Recognit, 12, 363-370.  
10215884 K.Ylinenjärvi, M.Widersten, and I.Björk (1999).
Hydrophobic sequences can substitute for the wild-type N-terminal sequence of cystatin A (stefin A) in tight binding to cysteine proteinases selection of high-affinity N-terminal region variants by phage display.
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10383426 M.Alvarez-Fernandez, A.J.Barrett, B.Gerhartz, P.M.Dando, J.Ni, and M.Abrahamson (1999).
Inhibition of mammalian legumain by some cystatins is due to a novel second reactive site.
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10410800 M.E.McGrath (1999).
The lysosomal cysteine proteases.
  Annu Rev Biophys Biomol Struct, 28, 181-204.  
10531502 M.Kozak, E.Jankowska, R.Janowski, Z.Grzonka, A.Grubb, M.Alvarez Fernandez, M.Abrahamson, and M.Jaskolski (1999).
Expression of a selenomethionyl derivative and preliminary crystallographic studies of human cystatin C.
  Acta Crystallogr D Biol Crystallogr, 55, 1939-1942.  
10430039 N.Kopitar-Jerala, R.Jerala, B.Turk, F.Gubensek, and V.Turk (1999).
Mutational analysis of two stefin A epitopes.
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10353845 S.Estrada, A.Pavlova, and I.Björk (1999).
The contribution of N-terminal region residues of cystatin A (stefin A) to the affinity and kinetics of inhibition of papain, cathepsin B, and cathepsin L.
  Biochemistry, 38, 7339-7345.  
9521728 A.Hall, I.Ekiel, R.W.Mason, F.Kasprzykowski, A.Grubb, and M.Abrahamson (1998).
Structural basis for different inhibitory specificities of human cystatins C and D.
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9860845 B.Gerhartz, I.Ekiel, and M.Abrahamson (1998).
Two stable unfolding intermediates of the disease-causing L68Q variant of human cystatin C.
  Biochemistry, 37, 17309-17317.  
  9524065 D.Turk, G.Guncar, M.Podobnik, and B.Turk (1998).
Revised definition of substrate binding sites of papain-like cysteine proteases.
  Biol Chem, 379, 137-147.  
9715907 E.Zerovnik, R.Jerala, R.Virden, L.Kroon Zitko, V.Turk, and J.P.Waltho (1998).
On the mechanism of human stefin B folding: II. Folding from GuHCl unfolded, TFE denatured, acid denatured, and acid intermediate states.
  Proteins, 32, 304-313.  
9493267 G.Guncar, M.Podobnik, J.Pungercar, B.Strukelj, V.Turk, and D.Turk (1998).
Crystal structure of porcine cathepsin H determined at 2.1 A resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function.
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PDB code: 8pch
9628031 H.Koiwa, R.E.Shade, K.Zhu-Salzman, L.Subramanian, L.L.Murdock, S.S.Nielsen, R.A.Bressan, and P.M.Hasegawa (1998).
Phage display selection can differentiate insecticidal activity of soybean cystatins.
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9585570 S.Estrada, M.Nycander, N.J.Hill, C.J.Craven, J.P.Waltho, and I.Björk (1998).
The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L.
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9632704 S.Halfon, J.Ford, J.Foster, L.Dowling, L.Lucian, M.Sterling, Y.Xu, M.Weiss, M.Ikeda, D.Liggett, A.Helms, C.Caux, S.Lebecque, C.Hannum, S.Menon, T.McClanahan, D.Gorman, and G.Zurawski (1998).
Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells.
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8995421 C.Illy, O.Quraishi, J.Wang, E.Purisima, T.Vernet, and J.S.Mort (1997).
Role of the occluding loop in cathepsin B activity.
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9151965 E.Zerovnik, R.Jerala, L.Kroon-Zitko, V.Turk, and K.Lohner (1997).
Characterization of the equilibrium intermediates in acid denaturation of human stefin B.
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9369956 G.S.Merz, E.Benedikz, V.Schwenk, T.E.Johansen, L.K.Vogel, J.I.Rushbrook, and H.M.Wisniewski (1997).
Human cystatin C forms an inactive dimer during intracellular trafficking in transfected CHO cells.
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  9012407 M.D.Lalioti, M.Mirotsou, C.Buresi, M.C.Peitsch, C.Rossier, R.Ouazzani, M.Baldy-Moulinier, A.Bottani, A.Malafosse, and S.E.Antonarakis (1997).
Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1).
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9362499 M.K.Safo, W.Z.Yang, L.Corselli, S.E.Cramton, H.S.Yuan, and R.C.Johnson (1997).
The transactivation region of the fis protein that controls site-specific DNA inversion contains extended mobile beta-hairpin arms.
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PDB code: 1f36
  9165062 W.Baumeister, Z.Cejka, M.Kania, and E.Seemüller (1997).
The proteasome: a macromolecular assembly designed to confine proteolysis to a nanocompartment.
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Friends and relations of the cystatin superfamily--new members and their evolution.
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8639676 D.B.Borza, F.M.Tatum, and W.T.Morgan (1996).
Domain structure and conformation of histidine-proline-rich glycoprotein.
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8654398 E.A.Auerswald, D.K.Nägler, S.Gross, I.Assfalg-Machleidt, M.T.Stubbs, C.Eckerskorn, W.Machleidt, and H.Fritz (1996).
Hybrids of chicken cystatin with human kininogen domain 2 sequences exhibit novel inhibition of calpain, improved inhibition of actinidin and impaired inhibition of papain, cathepsin L and cathepsin B.
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The importance of the second hairpin loop of cystatin C for proteinase binding. Characterization of the interaction of Trp-106 variants of the inhibitor with cysteine proteinases.
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Folding-related dimerization of human cystatin C.
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The crystal structure of the immunity protein of colicin E7 suggests a possible colicin-interacting surface.
  Proc Natl Acad Sci U S A, 93, 6437-6442.
PDB code: 1cei
  8929810 N.Cimerman, M.D.Kosorok, B.D.Korant, B.Turk, and V.Turk (1996).
Characterization of cystatin C from bovine parotid glands: cysteine proteinase inhibition and antiviral properties.
  Biol Chem Hoppe Seyler, 377, 19-23.  
  7540844 A.J.Pötgens, H.R.Westphal, R.M.de Waal, and D.J.Ruiter (1995).
The role of vascular permeability factor and basic fibroblast growth factor in tumor angiogenesis.
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7575236 A.Sharma, B.C.O'Connell, L.A.Tabak, and G.S.Bedi (1995).
Expression of a functional rat salivary cystatin S polypeptide in Escherichia coli.
  Arch Oral Biol, 40, 639-644.  
  7626231 B.Turk, J.G.Bieth, I.Björk, I.Dolenc, D.Turk, N.Cimerman, J.Kos, A.Colic, V.Stoka, and V.Turk (1995).
Regulation of the activity of lysosomal cysteine proteinases by pH-induced inactivation and/or endogenous protein inhibitors, cystatins.
  Biol Chem Hoppe Seyler, 376, 225-230.  
7671300 C.D.Mol, A.S.Arvai, R.J.Sanderson, G.Slupphaug, B.Kavli, H.E.Krokan, D.W.Mosbaugh, and J.A.Tainer (1995).
Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA.
  Cell, 82, 701-708.
PDB code: 1ugh
8747425 G.Lalmanach, C.Serveau, M.Brillard-Bourdet, J.R.Chagas, R.Mayer, L.Juliano, and F.Gauthier (1995).
Conserved cystatin segments as models for designing specific substrates and inhibitors of cysteine proteinases.
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Structural characterisation of human stefin A in solution and implications for binding to cysteine proteinases.
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Elongation on the amino-terminal part of stefin B decreases inhibition of cathepsin H.
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8427630 G.Lalmanach, J.Hoebeke, T.Moreau, M.Brillard-Bourdet, M.Ferrer-Ditt Martino, F.Borras-Cuesta, and F.Gauthier (1993).
Interaction between cystatin-derived peptides and papain.
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Recombinant chicken egg white cystatin variants of the QLVSG region.
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Calorimetric measurements of thermal denaturation of stefins A and B. Comparison to predicted thermodynamics of stefin-B unfolding.
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An immunochemical approach to investigating the mechanism of inhibition of cysteine proteinases by members of the cystatin superfamily.
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The complete primary structure of bovine stefin B.
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Natural protein proteinase inhibitors and their interaction with proteinases.
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Inactivation of human cystatin C and kininogen by human cathepsin D.
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  1868826 D.Musil, D.Zucic, D.Turk, R.A.Engh, I.Mayr, R.Huber, T.Popovic, V.Turk, T.Towatari, and N.Katunuma (1991).
The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity.
  EMBO J, 10, 2321-2330.
PDB code: 1huc
1879418 E.A.Auerswald, G.Genenger, R.Mentele, S.Lenzen, I.Assfalg-Machleidt, L.Mitschang, H.Oschkinat, and H.Fritz (1991).
Purification and characterization of a chicken egg white cystatin variant expressed in an Escherichia coli pIN-III-ompA system.
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1855589 V.Turk, and W.Bode (1991).
The cystatins: protein inhibitors of cysteine proteinases.
  FEBS Lett, 285, 213-219.  
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