Small Heat Shock Proteins (sHSPs) As Potential Drug Targets

Authors: Crabbe M.J.C.; Hepburne-Scott H.W.

Source: Current Pharmaceutical Biotechnology, Volume 2, Number 1, March 2001 , pp. 77-111(35)

Publisher: Bentham Science Publishers

Abstract:

Small heat shock proteins (sHSPs) belong to a family of 12- to 43-kDaproteins that are ubiquitous and are largely conserved in amino acid sequence among allorganisms.

The principal heat-shock proteins that have chaperone activity (that is, they protectnewly made proteins from misfolding) belong to five conserved classes HSP100,HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs). The sHSPs (which include alpha crystallin) can form large multimeric structures and have a wide range of cellular functions,including endowing cells with thermotolerance in vivo and being able to act as molecular chaperones in vitro sHSPs do this by forming stable complexes with folding -or unfolding- intermediates of their proteinsubstrates, probably the molten globule.

This paper includes a brief survey of the chaperone family, the small heat shock protein superfamily,transcription of sHSPs, sequence comparisons and structural models of small heat shock proteins - structuralelements as potential drug targets, sHSPs as chaperone-like proteins, alpha crystallin chaperone-like activity,conformational diseases - the role of alpha crystallin small heat shock protein superfamily proteins, post-translationalmodification and useful pharmacological agents.

Functionality of small heat shock proteins - targets and diseases where pharmacologically active agents are ofimportance, alpha crystallin- small heat shock proteins and prion diseases specific targets for diagnostic testsand drug development, details of some specific small heat shock proteins as drug targets, structural andfunctional implications for treatment.

Keywords: chaperone activity; Small Heat Shock Proteins; Drug Targets; HSP90; HSP70; HSP60; HSP100; Molecular Chaperones; Molecular Chaperones; Chaperone-like-protein; GroEL

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201013378833

Publication date: 2001-03-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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