Cystatins: biochemical and structural properties, and medical relevance.

  title={Cystatins: biochemical and structural properties, and medical relevance.},
  author={Vito Turk and Veronika Stoka and Du{\vs}an Turk},
  journal={Frontiers in bioscience : a journal and virtual library},
  • V. TurkV. StokaD. Turk
  • Published 1 May 2008
  • Biology, Chemistry
  • Frontiers in bioscience : a journal and virtual library
The cystatin superfamily comprises a large group of the cystatin domain containing proteins, present in a wide variety of organisms, including humans. Cystatin inhibitory activity is vital for the delicate regulation of normal physiological processes by limiting the potentially highly destructive activity of their target proteases such as the papain (C1) family, including cysteine cathepsins. Some of the cystatins also inhibit the legumain (C13) family of enzymes. Failures in biological… 

Figures from this paper

Modelling family 2 cystatins and their interaction with papain

Using interaction energy, HB and solvent accessible surface area analyses, a series of key residues that may be involved in papain–cystatin interaction are identified and will improve the understanding of fundamental inhibitory mechanisms of cystatin.

Mammalian cystatin and protagonists in brain diseases

The role of cystatins in neurological diseases is considered to be highly significant as it pave the way for commanding tool in the drug design.

Journey of cystatins from being mere thiol protease inhibitors to at heart of many pathological conditions

  • Anas ShamsiB. Bano
  • Biology, Chemistry
    International Journal of Biological Macromolecules
  • 2017

A Brief Account of Structure-Function Relationship of the Traditional Cysteine Protease Inhibitor - Cystatin with a Special Focus on Human Family 1 and 2 Cystatins

Crystallographic and mutagenesis studies identify three conserved regions mainly involved in the interaction with papain (C1) family of CPs, namely, N-terminal region, L1 loop, and (c) L2 loop, which determined the wide-ranging affinity of cystatins toward papain family ofCPs.

Physiological and Pathological Functions of Cysteine Cathepsins

This chapter presents an overview of the structure, synthesis, mode of action, regulation of expression and activity, and physiological as well as pathological role of lysosomal cysteine cathepsins.

Molecular Cloning and Characterization of Cystatin, a Cysteine Protease Inhibitor, from Bufo melanostictus

The novel cystatin cloned from a cDNA library of the skin of Bufo melanostictus can play an important role in host immunity and in the medical effect of B. melanstictus.

Functional characterization of single-domain cystatin-like cysteine proteinase inhibitors expressed by the trematode Fasciola hepatica

The aim of this work is to characterize the cystatin repertoire of F. hepatica, and to suggest that it is secreted by non-classical secretory pathway and that it may interact with host lysosomal cysteine proteinases.

Cysteine cathepsins and cystatins: from ancillary tasks to prominent status in lung diseases

A growing body of evidence supports the theory that cathepsins play specific functions in lung homeostasis and pathophysiological events such as asthma, lung fibrosis, chronic obstructive pulmonary disease, silicosis, bronchopulmonary dysplasia or tumor invasion.

Cystatins as regulators of cancer

Overexpression of cystatins has been found to inhibit metastasis and angiogenesis in certain cancers and may introduce future therapeutic advances in the control of cancer.

Cysteine cathepsins: From structure, function and regulation to new frontiers☆

  • V. TurkV. Stoka D. Turk
  • Biology, Chemistry
    Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
  • 2012



Crystal Structure of Human Cystatin D, a Cysteine Peptidase Inhibitor with Restricted Inhibition Profile*

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.

Structural Basis of Reduction-dependent Activation of Human Cystatin F*

Strikingly, core sugars for one of the two N-linked glycosylation sites of cystatin F are well ordered, and their conformation and interactions with the protein indicate that this unique feature of cyStatin F may modulate its inhibitory properties, in particular its reduced affinity toward asparaginyl endopeptidase compared with other cystatins.

Structural and functional characterization of two allelic variants of human cystatin D sharing a characteristic inhibition spectrum against mammalian cysteine proteinases.

The inhibitory properties displayed by cystatin D suggest that it has a function in saliva as inhibitor of either endogenous or exogenous enzymes with cathepsin S- or H-like properties.

Cystatin E is a Novel Human Cysteine Proteinase Inhibitor with Structural Resemblance to Family 2 Cystatins*

A strikingly high incidence of cystatin E clones in cDNA libraries from fetal skin epithelium and amniotic membrane cells indicates a protective role of cysteine proteinase inhibitor during fetal development.

Friends and relations of the cystatin superfamily—new members and their evolution

The new and older, established members of the cystatin “superfamily” are arranged into a possible evolutionary order, based on sequence homology and functional similarities.

Inhibition of Mammalian Legumain by Some Cystatins Is Due to a Novel Second Reactive Site*

Sequence alignments and molecular modeling led to the suggestion that a loop located on the opposite side to the papain-binding surface, between the α-helix and the first strand of the main β-pleated sheet of the cystatin structure, could be involved in legumain binding.

Evolution of proteins of the cystatin superfamily

The amino acid sequences of a number of proteins that have been suggested to be related to chicken cystatin, a protein from chicken egg white that inhibits cysteine proteinases, are examined and it is suggested that about 1000 million years ago a precursor containing disulfide loops appeared and that all disulfides-containing cystatins are derived from this.

A new subgroup of the family 2 cystatins

Emerging roles of cysteine cathepsins in disease and their potential as drug targets.

The current view on cathepsins as an emerging group of targets for several diseases and the development ofCathepsin K and S inhibitors for treatment of osteoporosis and various immune disorders are discussed.