A5053519410- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Signaling Pathways in Disease
- Blood properties and coagulation
- Histone Deacetylase Inhibitors Research
- Blood Coagulation and Thrombosis Mechanisms
- Cardiomyopathy and Myosin Studies
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Resistance in Bacteria
- Cardiovascular Function and Risk Factors
- Bacteriophages and microbial interactions
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- Glaucoma and retinal disorders
- DNA and Nucleic Acid Chemistry
- Bacterial Infections and Vaccines
- Congenital heart defects research
- Cholinesterase and Neurodegenerative Diseases
- Lipoproteins and Cardiovascular Health
- Biological Research and Disease Studies
- Marine Biology and Environmental Chemistry
- X-ray Diffraction in Crystallography
- Advanced Electron Microscopy Techniques and Applications
The University of Sydney
2016-2022
Universidade da Coruña
2005-2009
Consejo Superior de Investigaciones Científicas
2009
Instituto de Química Orgánica General
2005-2008
Centro de Investigaciones Biológicas Margarita Salas
2005-2008
Universidad de La Rioja
2008
Instituto de Química Física Blas Cabrera
2005-2008
National Institutes of Health
2002-2004
Laboratory of Molecular Genetics
2004
National Eye Institute
2004
Despite the importance of MYOC for glaucoma, protein's normal function(s) and pathogenic mechanism(s) mutations are not clear.Elevated intraocular pressure (IOP) glaucoma sometimes induced by corticosteroids, corticosteroid use can result in substantially increased expression.It has been suggested, therefore, that steroid-induced protein levels cause level-increasing contribute to associated with steroid use.A causative role elevated is controversial, however, it clear if IOP elevation.To...
Abstract Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and it unclear if conserved among the four remodeller families. Here we use single-molecule assays examine mechanism of action CHD4, which part least well understood family. We demonstrate that binding energy for CHD4-nucleosome complex formation—even in absence nucleotide—triggers significant conformational changes at entry side, effectively...
The nucleosome remodelling and deacetylase (NuRD) complex is essential for the development of animals. NuRD has roles in regulating gene expression repairing damaged DNA. comprises at least six proteins with two or more paralogues each protein routinely identified when purified from cell extracts. To understand structure function NuRD, a map direct subunit interactions needed. Dozens published studies have attempted to define inter-subunit connectivities. We propose that conclusions reported...
Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes involved in mitotic progression cranial-facial development. Here, using vitro assays, we show distinct domains of mediate binding free linker DNA as well H3K36me3 nucleosomes. In vivo, strongly recognizes regulatory regions weakly H3K36me3-containing gene bodies. Further, an MTA1-specific...
The nucleosome remodeling and deacetylase (NuRD) complex is essential for metazoan development but has been refractory to biochemical analysis. We present an integrated analysis of the native mammalian NuRD complex, combining quantitative mass spectrometry, cross-linking, protein biochemistry, electron microscopy define architecture complex. built from a 2:2:4 (MTA, HDAC, RBBP) module 1:1:1 (MBD, GATAD2, Chromodomain-Helicase-DNA-binding [CHD]) module, displays considerable structural...
The emergence of bacterial resistance to the major classes antibiotics has become a serious problem over recent years. For aminoglycosides, biochemical mechanism for is enzymatic modification drug. Interestingly, in several cases, oligosaccharide conformation recognized by ribosomic RNA and enzymes responsible antibiotic inactivation remarkably different. This observation suggests possible structure-based chemical strategy overcome resistance; principle, it should be design conformationally...
The nucleosome remodeling and deacetylase (NuRD) complex remodels the genome in context of both gene transcription DNA damage repair. It is essential for normal development distributed across multiple tissues organisms ranging from mammals to nematode worms. In common with other chromatin-remodeling complexes, however, its molecular mechanism action not well understood only limited structural information available show how assembled. As a step towards understanding structure NuRD complex, we...
Aminoglycosides are clinically relevant antibiotics that participate in a large variety of molecular recognition processes involving different RNA and protein receptors. The 3-D structures these policationic oligosaccharides play key role binding therefore determine their biological activity. Herein, we show the particular NH2/NH3+/OH distribution within antibiotic scaffold modulates oligosaccharide conformation flexibility. In particular, those polar groups flanking glycosidic linkages have...
Herein, we describe how the conformational differences exhibited by aminoglycosides in binding pockets of ribosome and those enzymes involved bacterial resistance can be exploited design new antibiotic derivatives with improved activity resistant strains. The simple modification shown figure, leading to conformationally restricted 5, provides an effective protection against aminoglycoside inactivation Staphylococcus aureus ANT4, both vivo vitro.
Commensal bacteria serve as an important line of defense against colonisation by opportunisitic pathogens, but the underlying molecular mechanisms remain poorly explored. Here, we show that strains a commensal bacterium, Haemophilus haemolyticus, make hemophilin, heme-binding protein inhibits growth opportunistic pathogen, non-typeable influenzae (NTHi) in culture. We purified NTHi-inhibitory from H. haemolyticus and identified hemophilin gene using proteomics knockout. An x-ray crystal...
The most significant mechanism of bacterial resistance to aminoglycosides is the enzymatic inactivation drug. Herein, we analyze several key aspects aminoglycoside recognition by enzyme ANT(4′) from Staphylococcus aureus, employing NMR complemented with site-directed mutagenesis experiments and measurements activity on newly synthesized kanamycin derivatives. From a methodological perspective, this analysis provides first example reported for use transferred NOE (trNOE) in complex molecular...
To characterize gene expression pattern in the combined tissues of rat iridocorneal angle by expressed sequence tag (EST) analysis, as part NEIBank project.RNA was extracted from dissected (iris, ciliary body, trabecular meshwork, and Schlemm's canal) used to construct unamplified, non-normalized cDNA libraries pSPORT1 vector. Approximately 5000 clones were sequenced 5'-end. Clones clustered identified using GRIST software, a procedure based on BLAST comparisons. Complete sequences several...
The aim of this study was to determine the effects forced expression myocd-A in left ventricular (LV) myocardium on cardiac performance early neonatal piglets. LV transfection with gene for homeodomain only protein (hop), an antagonist myocd-mediated activities, also performed. Gene delivery performed 6-day-old piglets using a low-traumatic, catheter-based, video-assisted procedure developed by us direct intra-myocardial injections plasmid DNA into 3-4 target areas ventral free wall (LVFW)....
The sequence information available for homeodomains reveals that salt bridges connecting pairs 19/30, 31/42, and 17/52 are frequent, whereas aliphatic residues at these sites rare mainly restricted to proteins from homeotherms. We have analyzed the influence of hydrophobic on stability DNA binding properties human Hesx-1 homeodomain. Regarding protein stability, our analysis shows side chains clearly preferred positions 19/30 31/42. This stabilizing results more favorable packing with core,...
New antifungals with unique modes of action are urgently needed to treat the increasing global burden invasive fungal infections. The inositol polyphosphate kinase (IPK) pathway, comprised IPKs that convert IP3 IP8, provides a promising new target due its impact on multiple, critical cellular functions and, unlike in mammalian cells, lack redundancy. Nearly all pathway essential for virulence, IP3-4 (IP3-4K) most critical. dibenzylaminopurine compound,...
Summary We showed that male-associated polypeptide (MAP) (Mikhailov et a1., 1995) identified in the gonad (mantle) tissue of Mytilus galloprovincialis is characterized by immunochemical similarity with protein ejaculatory bulb (esterase S) (Korochkin al., Drosophila virilis, belonging to carboxylesterase family. Accordingly, we addressed question concerning activity MAP and devised an approach substrate-specific situ detection mussel after SDS-PAGE. In this regard, demonstrated that: (1)...
Abstract Many commensal bacteria and opportunistic pathogens scavenge heme from their environment. Pathogens host are engaged in an arms race to control access heme, but similar conflicts between bacterial species that might regulate pathogen colonisation largely unknown. We show here a bacterium, Haemophilus haemolyticus , makes hemophilin, heme-binding protein not only allows the bacterium effectively for its own growth, also inhibits co-culture of pathogen, non-typeable influenzae (NTHi),...
ABSTRACT The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for development in animals but has been refractory to biochemical analysis. We present the first integrated analysis of architecture native mammalian NuRD complex, combining quantitative mass spectrometry, covalent cross-linking, protein biochemistry electron microscopy. built around a 2:2:4 pseudo-symmetric deacetylase module comprising MTA, HDAC RBBP subunits. This interacts asymmetrically with remodeling one...
A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly promyelocytic (M3). Eighteen ANLL have studied on admission, before chemotherapy was started. Levels antithrombin III (AT-III), protein C (PC), S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) fibrinogen (Fg) were determined. The results showed normal levels...