title: Pseudo-Contact NMR Shifts over the Paramagnetic Metalloprotein CoMMP-12 from First Principles.
abstract: 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 31413C 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.
authors: Institut für Chemie, Theoretische Chemie, Technische Universität Berlin, Sekr. C7, Straße des 17. Juni 135, 10623, Berlin, Germany.|Institut des Sciences Analytiques, UMR 5280 CNRS/ ENS Lyon/ UCB Lyon 1, 5 rue de la Doua, 69100, Villeurbanne, France.
authors: Ladislav
authors: L
authors: Benda
authors: NMR Research Unit, University of Oulu, P.O. Box 3000, 90014, Oulu, Finland.
authors: Jiří
authors: J
authors: Mareš
authors: Magnetic Resonance Center, University of Florence and, Interuniversity Consortium for Magnetic Resonance of Metalloproteins, Sesto Fiorentino, Italy.
authors: Enrico
authors: E
authors: Ravera
authors: Magnetic Resonance Center, University of Florence and, Interuniversity Consortium for Magnetic Resonance of Metalloproteins, Sesto Fiorentino, Italy.|Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors: Giacomo
authors: G
authors: Parigi
authors: Magnetic Resonance Center, University of Florence and, Interuniversity Consortium for Magnetic Resonance of Metalloproteins, Sesto Fiorentino, Italy.|Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors: Claudio
authors: C
authors: Luchinat
authors: Institut für Chemie, Theoretische Chemie, Technische Universität Berlin, Sekr. C7, Straße des 17. Juni 135, 10623, Berlin, Germany.
authors: Martin
authors: M
authors: Kaupp
authors: NMR Research Unit, University of Oulu, P.O. Box 3000, 90014, Oulu, Finland.
authors: Juha
authors: J
authors: Vaara
keywords: NMR spectroscopy; ab initio calculations; pseudo-contact shifts; susceptibility tensor