Cofactor fingerprinting with STD NMR to characterize proteins of unknown function: identification of a rare cCMP cofactor preference

Yao, Heng‐Chen; Sem, Daniel S.

doi:10.1016/j.febslet.2004.11.110

Cited by 13 publications

(6 citation statements)

References 27 publications

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“…By contrast, cIMP bound with submicromolar affinity to the GAF domains of PDE2 and PDE5 (Jäger et al 2010). The only GAF domain known so far that prefers cCMP over cAMP and cGMP is part of the protein RSP2 (radial spoke protein 2) from the green alga Chlamydomonas reinhardtii (Yao and Sem 2005). Interestingly, as discussed below, the same organism also contains a cCMP-hydrolyzing PDE activity, which, however, exhibits only very low cCMP affinity in the millimolar range (Fischer and Amrhein 1974).…”

Section: Traditional Classification Of Pdesmentioning

confidence: 93%

Inactivation of Non-canonical Cyclic Nucleotides: Hydrolysis and Transport

Schneider

Seifert

2016

Non-Canonical Cyclic Nucleotides

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This chapter addresses cNMP hydrolysis by phosphodiesterases (PDEs) and export by multidrug resistance associated proteins (MRPs). Both mechanisms are well-established for the canonical cNMPs, cAMP, and cGMP. Increasing evidence shows that non-canonical cNMPs (specifically cCMP, cUMP) are also PDE and MRP substrates. Hydrolysis of cUMP is achieved by PDE 3A, 3B, and 9A, which possibly explains the cUMP-degrading activities previously reported for heart, adipose tissue, and brain. Regarding cCMP, the only known "conventional" (class I) PDE that hydrolyzes cCMP is PDE7A. Older reports describe cCMP-degrading PDE-like activities in mammalian tissues, bacteria, and plants, but the molecular identity of these enzymes is not clear. High K and V values, insensitivity to common inhibitors, and unusually broad substrate specificities indicate that these activities probably do not represent class I PDEs. Moreover, the older results have to be interpreted with caution, since the historical analytical methods were not as reliable as modern highly sensitive and specific techniques like HPLC-MS/MS. Besides PDEs, the transporters MRP4 and 5 are of major importance for cAMP and cGMP disposal. Additionally, both MRPs also export cUMP, while cCMP is only exported by MRP5. Much less data are available for the non-canonical cNMPs, cIMP, cXMP, and cTMP. None of these cNMPs has been examined as MRP substrate. It was shown, however, that they are hydrolyzed by several conventional class I PDEs. Finally, this chapter reveals that there are still large gaps in our knowledge about PDE and MRP activities for canonical and non-canonical cNMPs. Future research should perform a comprehensive characterization of the known PDEs and MRPs with the physiologically most important cNMP substrates.

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Section: Traditional Classification Of Pdesmentioning

confidence: 93%

Inactivation of Non-canonical Cyclic Nucleotides: Hydrolysis and Transport

Schneider

Seifert

2016

Non-Canonical Cyclic Nucleotides

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“…One technique that was recently shown to be effective for establishing cofactor preferences for proteins is fingerprinting with saturation transfer difference (STD) NMR for detecting closely related cofactors. This approach was validated with both dehydrogenases and cyclic nucleotide-binding proteins (Yao and Sem 2005).…”

Section: A Brief Overview Of Proteomic Techniquesmentioning

confidence: 99%

Neuroproteomics as a promising tool in Parkinson’s disease research

2008

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Despite the vast number of studies on Parkinson's disease (PD), its effective diagnosis and treatment remains unsatisfactory. Hence, the relentless search for an optimal cure continues. The emergence of neuroproteomics, with its sophisticated techniques and non-biased ability to quantify proteins, provides a methodology with which to study the changes in neurons that are associated with neurodegeneration. Neuroproteomics is an emerging tool to establish disease-associated protein profiles, while also generating a greater understanding as to how these proteins interact and undergo post-translational modifications. Furthermore, due to the advances made in bioinformatics, insight is created concerning their functional characteristics. In this review, we first summarize the most prominent proteomics techniques and then discuss the major advances in the fast-growing field of neuroproteomics in PD. Ultimately, it is hoped that the application of this technology will lead towards a presymptomatic diagnosis of PD, and the identification of risk factors and new therapeutic targets at which pharmacological intervention can be aimed.

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“…In addition, STD NMR was used to refine crystal structures using only the strength of the STD signal in the absence of NOE data [141]. STD NMR can also be used to characterize enzymes and their preferences for cofactors since co-factors often bind to enzymes relatively weakly (K D > 1 µM) [142] [143]. In fact, STD-NMR has been used to screen proteins that bind to anesthetics to understand side effect profiles [144] and detect protons on substrate and products of enzymatic catalysis [145].…”

Section: Saturation Transfer Difference (Std) Nmr Screeningmentioning

confidence: 99%

Design of Inhibitors for S100B

Markowitz

MacKerell²,

Charpentier³

et al. 2005

CTMC

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S100B interacts with the p53 protein in a calcium-dependent manner and down-regulates its function as a tumor suppressor. Therefore, inhibiting the S100B-p53 interaction represents a new approach for restoring functional wild-type p53 in cancers with elevated S100B such as found in malignant melanoma. A discussion of the biological rational for targeting S100B and a description of methodologies relevant to the discovery of compounds that inhibit S100B-p53 binding, including computational techniques, structural biology techniques, and cellular assays, is presented.

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Cofactor fingerprinting with STD NMR to characterize proteins of unknown function: identification of a rare cCMP cofactor preference

Cited by 13 publications

References 27 publications

Inactivation of Non-canonical Cyclic Nucleotides: Hydrolysis and Transport

Inactivation of Non-canonical Cyclic Nucleotides: Hydrolysis and Transport

Neuroproteomics as a promising tool in Parkinson’s disease research

Design of Inhibitors for S100B

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