Search PubMed⌕ Search

Biomedical subjects

Chris Abell

Publications and source records attributed to Chris Abell.

46 records · Page 3Linked to original sources
PubMed2003

Comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily.

Escherichia coli ketopantoate hydroxymethyltransferase (KPHMT) catalyzes the first step in the biosynthesis pathway of pantothenate (vitamin B(5)), the transfer of a hydroxymethyl group onto alpha-ketoisovalerate. Here we describe a detailed comparative analysis of the KPHMT crystal structure and the identification of structural homologues, some of which have remarkable similarities in their active sites, modes of binding to substrates, and mechanisms. We show that KPHMT forms a family within the phosphoenolpyruvate/pyruvate superfamily. Based on the analysis, we propose that in this superfamily there should be a subdivision into two groups. This paper completes our structural analysis of the E. coli enzymes in the pantothenate pathway.

Amino Acid Sequence↗
PubMed2002

Writing with DNA and protein using a nanopipet for controlled delivery.

We present a new, general method for the controlled deposition of biological molecules on surfaces, based on a nanopipet operating in ionic solution. The potential applied to the pipet tip controls the flux of biological molecules from the pipet, allowing fine control of the delivery rate. We used the ion current to control the distance of the pipet from the surface of a glass slide and deposited the fluorescently labeled DNA or protein G at a defined location onto the surface. Features of 830 nm size were obtained by depositing the biotinylated DNA onto a streptavidin surface; 1.3 mum size spots were obtained by depositing protein G onto a positively charged glass surface.

DNA, Single-Stranded↗
PubMed2002

The structure and mechanism of the type II dehydroquinase from Streptomyces coelicolor.

The structure of the type II DHQase from Streptomyces coelicolor has been solved and refined to high resolution in complexes with a number of ligands, including dehydroshikimate and a rationally designed transition state analogue, 2,3-anhydro-quinic acid. These structures define the active site of the enzyme and the role of key amino acid residues and provide snap shots of the catalytic cycle. The resolution of the flexible lid domain (residues 21-31) shows that the invariant residues Arg23 and Tyr28 close over the active site cleft. The tyrosine acts as the base in the initial proton abstraction, and evidence is provided that the reaction proceeds via an enol intermediate. The active site of the structure of DHQase in complex with the transition state analog also includes molecules of tartrate and glycerol, which provide a basis for further inhibitor design.

Amino Acid Sequence↗
PubMed2002

High-throughput crystallography for lead discovery in drug design.

Knowledge of the three-dimensional structures of protein targets now emerging from genomic data has the potential to accelerate drug discovery greatly. X-ray crystallography is the most widely used technique for protein structure determination, but technical challenges and time constraints have traditionally limited its use primarily to lead optimization. Here, we describe how significant advances in process automation and informatics have aided the development of high-throughput X-ray crystallography, and discuss the use of this technique for structure-based lead discovery.

Crystallography↗
PubMed2002

The use of FTICR-MS to detect chemical tags from a combinatorial library.

The use of tagging in combinatorial chemistry permits tracking of the solid phase as it is taken through iterative split and mix cycles. Several analytical approaches to the identification of tags (and hence the chemical history of the support) have been described. We describe herein a novel chemical tagging strategy for combinatorial solid phase chemistry. The identities of the tags attached to a single bead are discovered by the high resolution, accurate mass technique of Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS).

Journal Article↗
PubMedDate not supplied

Calibration of AFM cantilever spring constants.

In this paper we present two simple, reliable and readily applicable methods for calibrating cantilevers and measuring the thickness of thin gold films. The spring constant calibration requires knowledge of the Young's modulus, density of the cantilever and resonant frequency. The thickness of thin gold layers was determined by measuring changes in the resonant frequency and Q-factor of beam shaped AFM cantilevers before and after coating. The techniques for measuring the spring constant and thin film thickness provide accuracy on the order of 10-15%.

Journal Article↗
PubMedDate not supplied

Chiral discrimination of basic and hydrophobic molecules by chemical force spectroscopy.

Chemical force spectroscopy (CFS) is becoming a powerful technique with which to measure intermolecular forces. The prime advantage over other techniques is the ability to map spatial distribution of ligands on the surface. We have used CFS to explore the binding force of a variety of different chiral molecules in order to understand more about the nature of what is a fundamental aspect of chemical biology and of central importance in pharmacology.

Journal Article↗