PDBsum entry 1rn7

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protein links
Protein binding PDB id
Jmol PyMol
Protein chain
112 a.a. *
Waters ×32
* Residue conservation analysis
PDB id:
Name: Protein binding
Title: Structure of human cystatin d
Structure: Cystatin d. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: parotid gland. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.50Å     R-factor:   0.191     R-free:   0.229
Authors: M.Alvarez-Fernandez,Y.H.Liang,M.Abrahamson,X.D.Su
Key ref:
M.Alvarez-Fernandez et al. (2005). Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile. J Biol Chem, 280, 18221-18228. PubMed id: 15728581 DOI: 10.1074/jbc.M411914200
30-Nov-03     Release date:   18-May-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P28325  (CYTD_HUMAN) -  Cystatin-D
142 a.a.
112 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     negative regulation of peptidase activity   2 terms 
  Biochemical function     protein binding     3 terms  


DOI no: 10.1074/jbc.M411914200 J Biol Chem 280:18221-18228 (2005)
PubMed id: 15728581  
Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.
M.Alvarez-Fernandez, Y.H.Liang, M.Abrahamson, X.D.Su.
Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared with its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S > cathepsin H > cathepsin L and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg(26)-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5- and 1.8-A resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel beta-sheet wrapped around a five-turn alpha-helix. The structures reveal differences in the peptidase-interacting regions when compared with other cystatins, providing plausible explanations for the restricted inhibitory specificity of cystatin D for some papain-like peptidases and its lack of reactivity toward legumain-related enzymes.
  Selected figure(s)  
Figure 3.
FIG. 3. The papain-binding sites of cystatin D and CEW cystatin. Stereo views of the aligned segments of human cystatin D (in magenta) and CEW cystatin (in cyan) involved in inhibition of C1 peptidases. A, front view of the first hairpin loop, L1. B, view of the second hairpin loop, L2, from the top (N-terminal end) of the aligned -helices. Labels are in the corresponding color.
Figure 4.
FIG. 4. The putative legumain-binding site of cystatin D and CEW cystatin. Stereo views of the back-side loops of cystatin D (in magenta) and CEW cystatin (in cyan). A, side view of the -helix end. B, view from the bottom of the -helix. Residue labels are in the same color as for the corresponding protein.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 18221-18228) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20189825 C.M.Ryan, P.Souda, F.Halgand, D.T.Wong, J.A.Loo, K.F.Faull, and J.P.Whitelegge (2010).
Confident assignment of intact mass tags to human salivary cystatins using top-down Fourier-transform ion cyclotron resonance mass spectrometry.
  J Am Soc Mass Spectrom, 21, 908-917.  
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
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
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.  
18632274 S.Zhu (2008).
Did cathelicidins, a family of multifunctional host-defense peptides, arise from a cysteine protease inhibitor?
  Trends Microbiol, 16, 353-360.  
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.