- Glycosylation and Glycoproteins Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
- Pancreatic function and diabetes
- Galectins and Cancer Biology
- Polysaccharides Composition and Applications
- Monoclonal and Polyclonal Antibodies Research
- Diet, Metabolism, and Disease
- Crystallography and molecular interactions
- Nonlinear Optical Materials Research
- Polysaccharides and Plant Cell Walls
- Crystal structures of chemical compounds
- Protein Structure and Dynamics
- Enzyme Production and Characterization
- Diabetes and associated disorders
- Neonatal and Maternal Infections
- Streptococcal Infections and Treatments
- Diet and metabolism studies
- Diabetes Management and Research
- Natural product bioactivities and synthesis
- Marine Sponges and Natural Products
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Proteoglycans and glycosaminoglycans research
University of Georgia
2012-2025
University of Copenhagen
2002-2004
University of Canterbury
1996-2002
Utrecht University
2002
University Medical Center Utrecht
2002
Indian Institute of Science Bangalore
1996-1998
Christ University
1996
Ordered water molecules bound to protein surfaces, or in protein−ligand interfaces, are frequently observed by crystallography. The investigation of the impact such conserved on stability and ligand affinity requires detailed structural, dynamic, thermodynamic analyses. Several crystal structures legume lectin concanavalin A (Con A) closely related carbohydrate ligands show presence a molecule that mediates binding. Experimental theoretical studies have examined role this complexation Con...
Glycan chains that terminate in sialic acid (Neu5Ac) are frequently the receptors targeted by pathogens for initial adhesion. Carbohydrate-binding proteins (lectins) with specificity Neu5Ac particularly useful detection and isolation of sialylated glycoconjugates, such as those associated pathogen adhesion well characteristic several diseases including cancer. Structural studies lectins essential order to understand origin their specificity, which is important when employing reagents...
Significance Cell-surface and secreted glycoproteins are initially synthesized glycosylated in the endoplasmic reticulum. Glycan structures trimmed remodeled as they transit secretory pathway, resulting multi-branched complex-type structures. The enzymes that remodel these have precise linkage branch specificities, with product of one reaction being specifically recognized substrate for following reaction. These reactions include N -acetylglucosaminyltransferase II (MGAT2), an enzyme...
Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse on cell surface and secreted glycoproteins. Additional modification of glycan core by α-1,6-fucose addition innermost GlcNAc residue (core fucosylation) is catalyzed an α-1,6-fucosyltransferase (FUT8). The importance fucosylation can be seen in complex pathological phenotypes FUT8 null mice, which display defects cellular signaling, development, subsequent neonatal lethality....
The intracellular environment is extremely crowded with macromolecules and filled compatible osmolytes, both of which are important features that favor the folded state proteins. This exerts a ubiquitous selective pressure in evolution protein function often ignored or neglected vitrostudies. As result, many proteins appear unstable exhibit poor kinetic parameters assays. Here, we use hydrodynamics to identify folding defect enzyme Nacetylglucosaminyltransferase II (MGAT2), show how it can...
The different tendencies of dinuclear azacryptates the m-CH2C6H4CH2 and 2,5-furano-spaced hosts L1 L2 to catalyse CO2 uptake-reactions within these sterically-protected host cavities are examined. Bridging methylcarbonates generated catalytically upon exposure methanol solutions L1, but not L2, di-transition cation cryptates atmospheric CO2. X-Ray crystallographic structures homodinuclear μ-carbonato both ligands μ-methylcarbonato with later first transition series cations reported. ESI-MS...
Allosteric feedback inhibition is the mechanism by which metabolic end products regulate their own biosynthesis binding to an upstream enzyme. Despite its importance in controlling metabolism, there are relatively few allosteric mechanisms understood detail. This because allostery does not have identifiable structural motif, making discovery of new enzymes a difficult process. The lack conserved motif implies that evolution each unique. Here we describe atypical human UDP-α-d-glucose...
Rhamnogalacturonan lyase (RG‐lyase) specifically recognizes and cleaves α‐1,4 glycosidic bonds between l ‐rhamnose d ‐galacturonic acids in the backbone of rhamnogalacturonan‐I, a major component plant cell wall polysaccharide, pectin. The three‐dimensional structure RG‐lyase from Aspergillus aculeatus has been determined to 1.5 Å resolution representing first known polysaccharide family 4 an enzyme with this catalytic specificity. 508‐amino acid polypeptide displays unique arrangement three...
Bacterial surface capsular polysaccharides (CPS) that are similar in carbohydrate sequence may differ markedly immunogenicity and antigenicity. The structural origin of these phenomena is poorly understood. Such a case presented by the Gram-positive bacteria Streptococcus agalactiae (Group B Streptococcus; GBS) type III (GBSIII) pneumoniae (Pn) 14 (Pn14), which share closely related CPS sequences. Nevertheless, antibodies (Abs) against GBSIII rarely cross-react with from Pn14. To establish...
Poly-N-acetyl-lactosamine (poly-LacNAc) structures are composed of repeating [-Galβ(1,4)-GlcNAcβ(1,3)-]
Evolutionarily conserved cysteine residues mediate the sensitivity of metabolic kinase FN3K to shifts in redox status.
UDP-α-d-xylose (UDX) acts as a feedback inhibitor of human UDP-α-d-glucose 6-dehydrogenase (hUGDH) by activating an unusual allosteric switch, the Thr131 loop. UDX binding induces loop to translate ∼5 Å through protein core, changing packing interactions and rotating helix (α6136–144) favor formation inactive hexameric complex. But how does conformational change occur given steric constraints core? To answer this question, we deleted Val132 from approximate intermediate state in transition....
Human UDP-α-d-glucose 6-dehydrogenase (hUGDH) forms a hexamer that catalyzes the NAD(+)-dependent oxidation of (UDG) to produce UDP-α-d-glucuronic acid. Mammalian UGDH displays hysteresis (observed as lag in progress curves), indicating enzyme undergoes slow transition from an inactive active state. Here we show hUGDH is sensitive product inhibition during lag. The results systematic decrease steady-state velocity and makes appear have second-order dependence on concentration. Using...
Human UDP-α-D-glucose dehydrogenase (hUGDH) catalyzes the NAD(+)-dependent oxidation of (UDG) to produce UDP-α-D-glucuronic acid. The oligomeric structure hUGDH is dynamic and can form two distinct hexameric complexes in solution. active consists dimers that undergo a concentration-dependent association hexamer with 32 symmetry. In presence allosteric feedback inhibitor UDP-α-D-xylose (UDX), changes shape an inactive, horseshoe-shaped complex. Previous studies have identified UDX-induced...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystal and Molecular Structure of Sclerophytin F Methyl Ether from the Soft Coral Cladiella krempfiNittala S. Sarma, Ramadas Chavakula, I. Nageswara Rao, Renuka Kadirvelraj, T. N. Guru Row, Isao SaitoCite this: J. Nat. Prod. 1993, 56, 11, 1977–1980Publication Date (Print):November 1, 1993Publication History Published online1 July 2004Published inissue 1 November...
Human UDP-α-d-glucose-6-dehydrogenase (hUGDH) displays hysteresis because of a slow isomerization from an inactive state (E*) to active (E). Here we show that the structure E* constrains hUGDH in conformation favors feedback inhibition at physiological pH. The inhibitor UDP-α-d-xylose (UDP-Xyl) competes with substrate UDP-α-d-glucose for site. Upon binding, UDP-Xyl triggers allosteric switch changes and affinity intersubunit interface form stable but horseshoe-shaped hexamer. Using...
Crystal structures of six binary salts involving aromatic amines as cations and hydrogen tartrates anions are presented. The materials 2,6-xylidinium-l-monohydrogen tartrate monohydrate, C12H18O6.5N, P22121, a = 7.283(2) Å, b 17.030(2) c 22.196(2) Z 8; 2,6-xylidinium-d-dibenzoyl monohydrogen tartrate, C26H25O8N, P21, 7.906(1) 24.757(1) 13.166(1) β 105.01(1)°, 4; 2,3-xylidinium-d-dibenzoyl C26H26O8.5N, 7.837(1) 24.488(1) 13.763(1) 105.69(1)°, 2-toluidinium-d-dibenzoyl C25H23O8N, P212121,...
Simple bromination of olefins almost invariably yields the trans-1,2-dibromo-product, and in many cases corresponding cis-product is an unknown compound. Approaches towards a reagent which will generally, mildly stereospecifically cis-brominate are now discussed. Manuscript received: 1 March 2001.
The man o' war (mow) phenotype in zebrafish is characterized by severe craniofacial defects due to a missense mutation UDP-α-d-xylose synthase (UXS), an essential enzyme proteoglycan biosynthesis. mow located the UXS dimer interface ∼16 Å away from active site, suggesting indirect effect on mechanism. We have examined structural and catalytic consequences of (R236H) soluble fragment human (hUXS), which shares 93% sequence identity with enzyme. In solution, hUXS dimers undergo...
Human UDP-glucose dehydrogenase (hUGDH) catalyzes the oxidation of into UDP-glucuronic acid, an essential substrate in Phase II metabolism drugs. hUGDH is a hexamer that exists equilibrium between active (E) state and inactive (EΩ) state, with latter being stabilized by binding allosteric inhibitor UDP-xylose (UDP-Xyl). The transition EΩ E slow can be observed as lag progress curves. Previous analysis suggested unliganded mainly EΩ, but two unique crystal forms suggest enzyme favors state....
Unusually long ( > 14 cm) crystalline needles grow from 4-(3-bromopropyloxy)salicylaldehyde 1 presumably as a consequence of Br⋯Br interactions; the powdered form shows one order magnitude greater SHG activity realtive to urea.