ProtMiscuity: a database of promiscuous proteins

Abstract Promiscuous behaviour in proteins and enzymes remains a challenging feature to understand the structure–function relationship. Here we present ProtMiscuity, a manually curated online database of proteins showing catalytic promiscuity. ProtMiscuity contains information about canonical and promiscuous activities comprising 88 different reactions in 57 proteins from 40 different organisms. It can be searched or browsed by protein names, organisms and descriptions of canonical and promiscuous reactions. Entries provide information on reaction substrates, products and kinetic parameters, mapping of active sites to sequence and structure and links to external resources with biological and functional annotations. ProtMiscuity could assist in studying the underlying mechanisms of promiscuous reactions by offering a unique and curated collection of experimentally derived data that is otherwise hard to find, retrieve and validate from literature.

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Substrate strain tunes operando geometric distortion and oxygen reduction activity of CuN2C2 single-atom sites

Nature Communications ◽

10.1038/s41467-021-26747-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Guokang Han ◽

Xue Zhang ◽

Wei Liu ◽

Qinghua Zhang ◽

Zhiqiang Wang ◽

...

Keyword(s):

Structure Function ◽

Oxygen Reduction ◽

Active Sites ◽

Geometric Distortion ◽

Single Atom ◽

Reduction Activity ◽

Activity Promotion ◽

Structure Function Relationship ◽

Substrate Strain ◽

Function Relationship

AbstractSingle-atom catalysts are becoming increasingly significant to numerous energy conversion reactions. However, their rational design and construction remain quite challenging due to the poorly understood structure–function relationship. Here we demonstrate the dynamic behavior of CuN2C2 site during operando oxygen reduction reaction, revealing a substrate-strain tuned geometry distortion of active sites and its correlation with the activity. Our best CuN2C2 site, on carbon nanotube with 8 nm diameter, delivers a sixfold activity promotion relative to graphene. Density functional theory and X-ray absorption spectroscopy reveal that reasonable substrate strain allows the optimized distortion, where Cu bonds strongly with the oxygen species while maintaining intimate coordination with C/N atoms. The optimized distortion facilitates the electron transfer from Cu to the adsorbed O, greatly boosting the oxygen reduction activity. This work uncovers the structure–function relationship of single-atom catalysts in terms of carbon substrate, and provides guidance to their future design and activity promotion.

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Seeking a Structure-Function Relationship for γ-Al2O3 Surfaces

10.26434/chemrxiv.6789974.v1 ◽

2018 ◽

Author(s):

Muhammed Acikgoz ◽

Jaren Harrell ◽

Michele Pavanello

Keyword(s):

Structure Function ◽

Active Sites ◽

Chemical Reactivity ◽

Surface Oxidation ◽

Morphological Variations ◽

Structure Function Relationship ◽

Interesting Correlation ◽

Surface Dipole ◽

New Perspective ◽

Function Relationship

<p>The subject of this work is gamma alumina surfaces. We show that surface morphological variations can induce significant changes in work function and surface dipole particularly in regards of the surface oxidation level.</p> <p>Our results offer a new perspective on the structure-function relationship between surface morphology and electronic properties. For example, and for the first time in the literature, we uncover an interesting correlation between surface dipole and chemical reactivity of the surface active sites.</p>

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Mechanism of HIV-1 Resistance to Short-Peptide Fusion Inhibitors Targeting the Gp41 Pocket

Journal of Virology ◽

10.1128/jvi.00373-15 ◽

2015 ◽

Vol 89 (11) ◽

pp. 5801-5811 ◽

Cited By ~ 23

Author(s):

Yang Su ◽

Huihiui Chong ◽

Zonglin Qiu ◽

Shengwen Xiong ◽

Yuxian He

Keyword(s):

Structure Function ◽

Heptad Repeat ◽

Cross Resistance ◽

Short Peptide ◽

Fusion Inhibitors ◽

Structure Function Relationship ◽

Underlying Mechanisms ◽

Function Relationship ◽

Relationship Of ◽

Hiv 1

ABSTRACTThe deep hydrophobic pocket on the N trimer of HIV-1 gp41 has been considered an ideal drug target. On the basis of the M-T hook structure, we recently developed short-peptide-based HIV-1 fusion inhibitors (MTSC22 and HP23), which mainly target the pocket site and possess highly potent antiviral activity. In this study, we focused on investigating their resistance pathways and mechanisms by escape HIV-1 mutants to SC22EK, a template peptide for MTSC22 and HP23. Two substitutions, E49K and N126K, located, respectively, at the N- and C-heptad repeat regions of gp41, were identified as conferring high resistance to the inhibitors targeting the pocket and cross-resistance to enfuvirtide (T20) and sifuvirtide (SFT). The underlying mechanisms of SC22EK-induced resistance include the following: (i) significantly reduced binding affinity of the inhibitors, (ii) dramatically enhanced interaction of the viral six-helix bundle, and (iii)severely damaged functionality of the viral Env complex. Our data have provided important information for the structure-function relationship of gp41 and the structure-activity relationship of viral fusion inhibitors.IMPORTANCEEnfuvirtide (T20) is the only HIV-1 fusion inhibitor in clinical use, but the problem of resistance significantly limits its use, calling for new strategies or concepts to develop next-generation drugs. On the basis of the M-T hook structure, short-peptide HIV-1 fusion inhibitors specifically targeting the gp41 pocket site exhibit high binding and antiviral activities. Here, we investigated the molecular pathway of HIV-1 resistance to the short inhibitors by selecting and mapping the escape mutants. The key substitutions for resistance and the underlying mechanisms have been finely characterized. The data provide important information for the structure-function relationship of gp41 and its inhibitors and will definitely help our future development of novel drugs that block gp41-dependent fusion.

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Stepwise Assembly of Heterobimetallic Complexes: Synthesis, Structure, and Physical Properties

Dalton Transactions ◽

10.1039/d1dt01021b ◽

2021 ◽

Author(s):

Justin L Lee ◽

Victoria Frances Oswald ◽

Saborni Biswas ◽

Ethan A Hill ◽

Joseph W Ziller ◽

...

Keyword(s):

Physical Properties ◽

Structure Function ◽

Active Sites ◽

Heterobimetallic Complexes ◽

Structure Function Relationship ◽

Function Relationship ◽

Stepwise Assembly ◽

Synthetic Models

Bimetallic active sites are ubiquitous in metalloenzymes and has sparked investigations of synthetic models to aid in the establishment of structure-function relationship. We previously reported a series of discrete bimetallic...

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Seeking a Structure-Function Relationship for γ-Al2O3 Surfaces

10.26434/chemrxiv.6789974 ◽

2018 ◽

Author(s):

Muhammed Acikgoz ◽

Jaren Harrell ◽

Michele Pavanello

Keyword(s):

Structure Function ◽

Active Sites ◽

Chemical Reactivity ◽

Surface Oxidation ◽

Morphological Variations ◽

Structure Function Relationship ◽

Interesting Correlation ◽

Surface Dipole ◽

New Perspective ◽

Function Relationship

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Mouse models to study von Willebrand factor structure-function relationships in vivo

Hämostaseologie ◽

10.1055/s-0037-1616933 ◽

2009 ◽

Vol 29 (01) ◽

pp. 17-20 ◽

Cited By ~ 2

Author(s):

I. Marx ◽

I. Badirou ◽

R. Pendu ◽

O. Christophe ◽

C. V. Denis

Keyword(s):

Structure Function ◽

Transient Expression ◽

Von Willebrand Factor ◽

Large Size ◽

Mouse Hepatocytes ◽

Function Relationship ◽

Von Willebrand ◽

Willebrand Factor

SummaryVon Willebrand factor (VWF) structure-function relationship has been studied only through in vitro approaches. The VWF-deficient mouse model has been extremely useful to examine the in vivo function of VWF but does not allow a more subtle analysis of the relative importance of its different domains. However, considering the large size of VWF and its capacity to interact with various ligands in order to support platelet adhesion and aggregation, the necessity to evaluate independently these interactions appeared increasingly crucial. A recently developed technique, known as hydrodynamic injection, which allows transient expression of a transgene by mouse hepatocytes, proved very useful in this regard. Indeed, transient expression of various VWF mutants in VWF-deficient mice contributed to improve our knowledge about the role of VWF interaction with subendothelial collagens and with platelets receptors in VWF roles in haemostasis and thrombosis. These findings can provide new leads in the development of anti-thrombotic therapies.

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