SUMO protease SENP1 induces isomerization of the scissile peptide bond

Shen, Linnan, Tatham, Michael H, Dong, Changjiang, Zagórska, Anna, Naismith, James H and Hay, Ronald T (2006) SUMO protease SENP1 induces isomerization of the scissile peptide bond. Nature Structural & Molecular Biology, 13 (12). pp. 1069-77. ISSN 1545-9993

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Abstract

Small ubiquitin-like modifier (SUMO)-specific protease SENP1 processes SUMO-1, SUMO-2 and SUMO-3 to mature forms and deconjugates them from modified proteins. To establish the proteolytic mechanism, we determined structures of catalytically inactive SENP1 bound to SUMO-1-modified RanGAP1 and to unprocessed SUMO-1. In each case, the scissile peptide bond is kinked at a right angle to the C-terminal tail of SUMO-1 and has the cis configuration of the amide nitrogens. SENP1 preferentially processes SUMO-1 over SUMO-2, but binding thermodynamics of full-length SUMO-1 and SUMO-2 to SENP1 and K(m) values for processing are very similar. However, k(cat) values differ by 50-fold. Thus, discrimination between unprocessed SUMO-1 and SUMO-2 by SENP1 is based on a catalytic step rather than substrate binding and is likely to reflect differences in the ability of SENP1 to correctly orientate the scissile bonds in SUMO-1 and SUMO-2.

Item Type: Article
Uncontrolled Keywords: catalysis,crystallography, x-ray,cysteine,endopeptidases,gtpase-activating proteins,humans,isoenzymes,kinetics,models, molecular,peptides,protein binding,protein structure, quaternary,sumo-1 protein,substrate specificity,thermodynamics
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 17 Nov 2014 12:58
Last Modified: 21 Apr 2020 23:36
URI: https://ueaeprints.uea.ac.uk/id/eprint/50984
DOI: 10.1038/nsmb1172

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