University of Oulu

L. Benda, J. Mareš, E. Ravera, G. Parigi, C. Luchinat, M. Kaupp, J. Vaara, Angew. Chem. Int. Ed. 2016, 55, 14713

Pseudo-contact NMR shifts over the paramagnetic metalloprotein CoMMP-12 from first principles

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Author: Benda, Ladislav1,2; Mareš, Jiří3; Ravera, Enrico4;
Organizations: 1Technische Universität Berlin Institut für Chemie, Theoretische Chemie Berlin Germany
2UMR 5280 CNRS/ ENS Lyon/ UCB Lyon 1 Institut des Sciences Analytiques Villeurbanne France
3University of Oulu NMR Research Unit Oulu Finland
4University of Florence and Interuniversity Consortium for Magnetic Resonance of Metalloproteins Magnetic Resonance Center Sesto Fiorentino Italy
5University of Florence Department of Chemistry Sesto Fiorentino Italy
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: John Wiley & Sons, 2016
Publish Date: 2018-01-03


Long-range pseudo-contact NMR shifts (PCSs) provide important restraints for the structure refinement of proteins when a paramagnetic metal center is present, either naturally or introduced artificially. Here we show that ab initio quantum-chemical methods and a modern version of the Kurland–McGarvey approach for paramagnetic NMR (pNMR) shifts in the presence of zero-field splitting (ZFS) together provide accurate predictions of all PCSs in a metalloprotein (high-spin cobalt-substituted MMP-12 as a test case). Computations of 314 ¹³C PCSs using g- and ZFS tensors based on multi-reference methods provide a reliable bridge between EPR-parameter- and susceptibility-based pNMR formalisms. Due to the high sensitivity of PCSs to even small structural differences, local structures based either on X-ray diffraction or on various DFT optimizations could be evaluated critically by comparing computed and experimental PCSs. Many DFT functionals provide insufficiently accurate structures. We also found the available 1RMZ PDB X-ray structure to exhibit deficiencies related to binding of a hydroxamate inhibitor. This has led to a newly refined PDB structure for MMP-12 (5LAB) that provides a more accurate coordination arrangement and PCSs.

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Series: Angewandte chemie international edition in English
ISSN: 1433-7851
ISSN-E: 1521-3773
ISSN-L: 1433-7851
Volume: 55
Issue: 47
Pages: 14713 - 14717
DOI: 10.1002/anie.201608829
Type of Publication: A1 Journal article – refereed
Field of Science: 116 Chemical sciences
114 Physical sciences
Funding: This work has been carried out within the framework of the pNMR initial training network (Marie Curie Actions,EUSeventh Framework Programme,FP7/2007–2013, REA grant no.317127). Further support by the UniCat Berlin DFG excellence cluster (for L.B.and M.K.) and the Academy of Finland (for J.M. and J.V. ) is acknowledged. Thework was also supported by Ente Cassa di Risparmio di Firenze,MIUR PRIN 2012SK7ASN,and CERM, part of the European Strategy Forum on Research Infrastructures (ESFRI).
EU Grant Number: (317127) PNMR - Pushing the Envelope of Nuclear Magnetic Resonance Spectroscopy for Paramagnetic Systems. A Combined Experimental and Theoretical Approach
Copyright information: © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: L. Benda, J. Mareš, E. Ravera, G. Parigi, C. Luchinat, M. Kaupp, J. Vaara, Angew. Chem. Int. Ed. 2016, 55, 14713, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.