Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP

CRM1 is a nuclear export receptor that has been intensively targeted over the last decade for the development of antitumor and antiviral drugs. Structural analysis of several inhibitor compounds bound to CRM1 revealed that their mechanism of action relies on the covalent modification of a critical c...

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Autores principales: Shaikhqasem, Alaa, Schmitt, Kerstin, Valerius, Oliver, Ficner, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2021
Materias:
Research Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938638/
https://www.ncbi.nlm.nih.gov/pubmed/33682791
http://dx.doi.org/10.1107/S2053230X2100203X
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author Shaikhqasem, Alaa
Schmitt, Kerstin
Valerius, Oliver
Ficner, Ralf
author_facet Shaikhqasem, Alaa
Schmitt, Kerstin
Valerius, Oliver
Ficner, Ralf
author_sort Shaikhqasem, Alaa
collection PubMed
description CRM1 is a nuclear export receptor that has been intensively targeted over the last decade for the development of antitumor and antiviral drugs. Structural analysis of several inhibitor compounds bound to CRM1 revealed that their mechanism of action relies on the covalent modification of a critical cysteine residue (Cys528 in the human receptor) located in the nuclear export signal-binding cleft. This study presents the crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP at 2.58 Å resolution. The results demonstrate that buffer components can interfere with the characterization of cysteine-dependent inhibitor compounds.
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spelling pubmed-79386382021-03-10 Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP Shaikhqasem, Alaa Schmitt, Kerstin Valerius, Oliver Ficner, Ralf Acta Crystallogr F Struct Biol Commun Research Communications CRM1 is a nuclear export receptor that has been intensively targeted over the last decade for the development of antitumor and antiviral drugs. Structural analysis of several inhibitor compounds bound to CRM1 revealed that their mechanism of action relies on the covalent modification of a critical cysteine residue (Cys528 in the human receptor) located in the nuclear export signal-binding cleft. This study presents the crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP at 2.58 Å resolution. The results demonstrate that buffer components can interfere with the characterization of cysteine-dependent inhibitor compounds. International Union of Crystallography 2021-03-03 /pmc/articles/PMC7938638/ /pubmed/33682791 http://dx.doi.org/10.1107/S2053230X2100203X Text en © Shaikhqasem et al. 2021 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Communications
Shaikhqasem, Alaa
Schmitt, Kerstin
Valerius, Oliver
Ficner, Ralf
Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP
title Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP
title_full Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP
title_fullStr Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP
title_full_unstemmed Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP
title_short Crystal structure of human CRM1, covalently modified by 2-mercaptoethanol on Cys528, in complex with RanGTP
title_sort crystal structure of human crm1, covalently modified by 2-mercaptoethanol on cys528, in complex with rangtp
topic Research Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938638/
https://www.ncbi.nlm.nih.gov/pubmed/33682791
http://dx.doi.org/10.1107/S2053230X2100203X
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