A key tyrosine substitution restricts nucleotide hydrolysis by the ectoenzyme <scp>NPP</scp>5

Gorelik, A.; Randriamihaja, A.; Illés, K.; Nagar, Bhushan

doi:10.1111/febs.14266

Cited by 28 publications

(23 citation statements)

References 40 publications

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“…(2017) PDBID: 5N92 Protein Structure De Nardis et al. (2017) PDBID: 5NSC Protein Structure Gorelik et al. (2017) PDBID: 5VEM Protein Structure Cingolani et al.…”

Section: Methodsmentioning

confidence: 99%

Automatically Fixing Errors in Glycoprotein Structures with Rosetta

et al. 2019

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Summary Recent advances in single-particle cryo-electron microscopy (cryoEM) have resulted in determination of an increasing number of protein structures with resolved glycans. However, existing protocols for the refinement of glycoproteins at low resolution have failed to keep up with these advances. As a result, numerous deposited structures contain glycan stereochemical errors. Here, we describe a Rosetta-based approach for both cryoEM and X-ray crystallography refinement of glycoproteins which is capable of correcting conformational and configurational errors in carbohydrates. Building upon a previous Rosetta framework, we introduced additional features and score terms enabling automatic detection, setup and refinement of glycan-containing structures. We benchmarked this approach using twelve crystal structures and showed that glycan geometries can be automatically improved while maintaining good fit to the crystallographic data. Finally, we used this method to refine carbohydrates of the human coronavirus NL63 spike glycoprotein and of an HIV envelope glycoprotein, demonstrating its usefulness for cryoEM refinement.

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“…(2017) PDBID: 5N92 Protein Structure De Nardis et al. (2017) PDBID: 5NSC Protein Structure Gorelik et al. (2017) PDBID: 5VEM Protein Structure Cingolani et al.…”

Section: Methodsmentioning

confidence: 99%

Automatically Fixing Errors in Glycoprotein Structures with Rosetta

et al. 2019

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“…Unlike all other members of the NPP family, the conserved nucleophilic residue in the active site of NPP6 is a serine instead of a threonine. Finally, NPP7 (or alkaline sphingomyelinase) is involved in the digestion of the dietary fat sphingomyelin (Duan et al, 2003), whereas the substrates of NPP5 remain unknown (Gorelik, Randriamihaja et al, 2017). Of note, the structural organization of these enzymes (shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…NPP4, NPP5, NPP6 and NPP7 are type I transmembrane ecto-enzymes. Lacking the N-terminal SMB domains, they consist of a catalytic PDE domain followed by a transmembrane helix C-terminal region (NPP4, NPP5 and NPP7) or a GPI anchor (NPP6) (Albright et al, 2014;Gorelik, Randriamihaja et al, 2017;Morita et al, 2016;Gorelik, Liu et al, 2017). The expression of a proteolytic product of NPP7 secreted in the lumen has also been described (Wu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Structure of a nucleotide pyrophosphatase/phosphodiesterase (NPP) fromEuphorbia characiaslatex characterized by small-angle X-ray scattering: clues for the general organization of plant NPPs

Sabatucci

Pintus

Cabras

et al. 2020

Acta Cryst Sect D Struct Biol

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Little information is available concerning the structural features of nucleotide pyrophosphatase/phosphodiesterases (NPPs) of plant origin and the crystal structures of these proteins have not yet been reported. The aim of this study was to obtain insight into these aspects by carrying out a comparative analysis of the sequences of two different fragments of an NPP from the latex of the Mediterranean shrub Euphorbia characias (ELNPP) and by studying the low-resolution structure of the purified protein in solution by means of small-angle X-ray scattering. This is the first structure of a plant NPP in solution that has been reported to date. It is shown that the ELNPP sequence is highly conserved in many other plant species. Of note, the catalytic domains of these plant NPPs have the same highly conserved PDE-domain organization as mammalian NPPs. Moreover, ELNPP is a dimer in solution and this oligomerization state is likely to be common to other plant enzymes.

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“…Despite these multiple possible roles, the biochemistry of NPP3 has not been extensively characterized, and the determinants of its substrate specificity are unknown. The 3D structures of all the other mammalian NPPs have been elucidated [11,[22][23][24][25][26][27][28], whereas NPP3 has been the subject of modeling studies to assist isozyme-specific inhibitor design [29][30][31]. Here, we report the crystal structure of human NPP3 as well as its complex with a substrate analog, and explore the dimerization properties of this enzyme.…”

Section: Introductionmentioning

confidence: 99%