A5065753850- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Toxin Mechanisms and Immunotoxins
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Folate and B Vitamins Research
- Monoclonal and Polyclonal Antibodies Research
- X-ray Diffraction in Crystallography
- Enzyme-mediated dye degradation
- Microbial Metabolic Engineering and Bioproduction
- Crystallization and Solubility Studies
- Signaling Pathways in Disease
- Crystallography and molecular interactions
- Protein purification and stability
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Properties of Aromatic Compounds
- Nonlinear Optical Materials Research
- Supramolecular Chemistry and Complexes
- Photosynthetic Processes and Mechanisms
- Enzyme Structure and Function
- melanin and skin pigmentation
- Sulfur Compounds in Biology
- Plant biochemistry and biosynthesis
- Click Chemistry and Applications
CIC bioGUNE
2020-2024
Boeing (Spain)
2021
Digital Research Alliance of Canada
2021
Euskadiko Parke Teknologikoa
2021
Universidad de Sevilla
2017
Natural proteins are highly optimized for function but often difficult to produce at a scale suitable biotechnological applications due poor expression in heterologous systems, limited solubility, and sensitivity temperature. Thus, general method that improves the physical properties of native while maintaining could have wide utility protein-based technologies. Here, we show deep neural network ProteinMPNN, together with evolutionary structural information, provides route increasing protein...
The interaction of human galectin-1 with a variety oligosaccharides, from di-(N-acetyllactosamine) to tetra-saccharides (blood B type-II antigen) has been scrutinized by using combined approach different NMR experiments, molecular dynamics (MD) simulations, and isothermal titration calorimetry. Ligand- receptor-based experiments assisted computational methods allowed proposing three-dimensional structures for the complexes, which explained lack enthalpy gain when increasing chemical...
Laccases are in increasing demand as innovative solutions the biorefinery fields. Here, we combine mutagenesis with structural, kinetic, and silico analyses to characterize molecular features that cause evolution of a hyperthermostable metallo-oxidase from multicopper oxidase family into laccase (kcat 273 s–1 for bulky aromatic substrate). We show six mutations scattered across enzyme collectively modulate dynamics improve binding catalysis substrate. The replacement residues during early...
Abstract Natural proteins are highly optimized for function, but often difficult to produce at a scale suitable biotechnological applications due poor expression in heterologous systems, limited solubility, and sensitivity temperature. Thus, general method that improves the physical properties of native while maintaining function could have wide utility protein-based technologies. Here we show deep neural network ProteinMPNN together with evolutionary structural information provides route...
Human sialic acid binding immunoglobulin-like lectin-8 (Siglec-8) is an inhibitory receptor that triggers eosinophil apoptosis and can inhibit mast cell degranulation when engaged by specific monoclonal antibodies (mAbs) or sialylated ligands. Thus, Siglec-8 has emerged as a critical negative regulator of inflammatory responses in diverse diseases, such allergic airway inflammation. Herein, we have deciphered the molecular recognition features interaction with mAb lirentelimab (2C4, under...
The chemistry of diazo compounds has generated a huge breadth applications in the field organic synthesis. Their versatility combined with their tunable reactivity, stability, and chemoselectivity makes desirable reagents for chemical biologists. Here, we describe method precise installation handles on proteins antibodies mild specific approach. Subsequent 1,3-cycloaddition reactions strained alkynes enable both bioimaging through an in-cell "click" reaction probing cysteine proteome cell...
The tandem-repeat Galectin-4 (Gal-4) contains two different domains covalently linked through a short flexible peptide. Both have been shown to bind preferentially A and B histo blood group antigens with affinities, although the binding details are not yet available. biological relevance of these associations is unknown, it could be related its attributed role in pathogen recognition. presentation terms peripheral core structures differs among tissues from that antigen-mimicking produced by...
Abstract Pharmaceutical industry is progressively replacing the chemical synthesis of cholesterol‐lowering agents by enzymatic processes. The directed evolution acyltransferase LovD was a breakthrough in simvastatin, although little known about how vitro path raised up an engineered variant (LovD9) with excellent biocatalytic properties (high catalytic efficiency and stability under reaction conditions). In this study, we unveil different mutation clusters scattered across LovD9 primary...
NMR, ITC, and MD data show that the two domains of human galectin-8 independently recognize sialyl- fucosyl-containing glycans.
Cysteine plays a major role in the redox homeostasis and antioxidative defense mechanisms of many parasites phylum Apicomplexa. Of relevance to human health is Toxoplasma gondii, causative agent toxoplasmosis. A route cysteine biosynthesis this parasite reverse transsulfuration pathway involving two key enzymes cystathionine β-synthase (CBS) γ-lyase (CGL). CBS from T. gondii (TgCBS) catalyzes pyridoxal-5́-phosphate-dependent condensation homocysteine with either serine or O-acetylserine...
Artificial intelligence-based protein structure prediction methods such as AlphaFold2 have emerged powerful tools for characterizing proteins sequence-structure relationship offering unprecedented opportunities the molecular interpretation of biological and biochemical phenomena. While initially confined to providing a static representation through their global free-energy minimum, has demonstrated ability partially sample conformational landscapes, insights into dynamics, which is...
Protein A075L is a β-xylosyltransferase that participates in producing the core of N-glycans found VP54, major viral capsid protein Paramecium bursaria chlorella virus-1 (PBCV-1). In this study, we present an X-ray crystallographic analysis apo form A075L, along with its complexes sugar donor and trisaccharide acceptor. The structure shows typical GT-B folding, two Rossmann-like fold domains, which acceptor substrate binds to N-terminal region, nucleotide-sugar C-terminal region. We propose...
Abstract The interplay between noncovalent interactions that involve oxygenated heteroaromatic rings have been studied for the first time in this work. In particular, we report an advance knowledge‐based anion–π together with (C−H) + ⋅⋅⋅anion contacts. To understand how anion modulates these interactions, synthesis of pyrylium salts a variety anions was performed by using anionic metathesis methodology. synthesized complexes were classified series, example, derived from halogens, oxoacids,...
This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by laboratory evolved acyltransferase LovD9. Vinyl and p-nitrophenyl esters have emerged as alternate substrates LovD9-catalyzed acylation. While vinyl can reach product yields high ones obtained α-dimethyl butyryl-S-methyl-3-mercaptopropionate (DMB-SMMP), thioester which LovD9 was evolved, display a reactivity even higher than DMB-SMMP first step yet yield is lower. The...
Abstract Invited for the cover of this issue are groups Gonzalo Jiménez‐Osés and Fernando López‐Gallego at CIC bioGUNE biomaGUNE, respectively. The image depicts substrate scope an engineered acyl transferases synthesis statin derivatives. Read full text article 10.1002/chem.202300911 .
ABSTRACT Recombinant proteins and antibodies are routinely used as drugs to treat prevalent diseases such diabetes or cancer, while enzyme replacement gene therapies the main therapeutic intervention lines in rare diseases. In protein-based therapeutics, optimized vivo stability is key intrinsic denaturation intracellular proteostatic degradation will limit potency, particularly treatments requiring a sustained action, clearance mechanisms may amount of circulating protein. ultimately...
This article presents an overview of recent computational studies dedicated to the analysis binding between galectins and small-molecule ligands. We first present a summary most popular simulation techniques adopted for calculating poses energies then discuss relevant examples reported in literature three main classes (dimeric, tandem, chimera). show that galectin-ligand interactions is mature field has proven invaluable completing unraveling experimental observations. Future perspectives...
A multidisciplinary study is presented to shed light on how pyrylium frameworks, as π-hole donors, establish π-π interactions. The combination of CSD analysis, computational modelling (ab intitio, DFT and MD simulations) experimental NMR spectroscopy data provides essential information the key parameters that characterize these intereactions, opening new avenues for further applications this versatile heterocycle.
ABSTRACT Cystathionine β-synthase (CBS), the pivotal enzyme of reverse transsulfuration pathway, catalyzes pyridoxal-5’-phosphate-dependent condensation serine with homocysteine to form cystathionine. Additionally, CBS performs alternative reactions that use and cysteine as substrates leading endogenous biosynthesis hydrogen sulfide (H 2 S), an important signal transducer in many physiological pathological processes. Toxoplasma gondii, causative agent toxoplasmosis, encodes a functional ( Tg...