A5051578001- Protein Interaction Studies and Fluorescence Analysis
- Trace Elements in Health
- Drug Transport and Resistance Mechanisms
- Blood properties and coagulation
- Ion channel regulation and function
- Electron Spin Resonance Studies
- Magnesium in Health and Disease
- Alkaline Phosphatase Research Studies
- Lanthanide and Transition Metal Complexes
- Metal complexes synthesis and properties
- Cardiac electrophysiology and arrhythmias
- Hypothalamic control of reproductive hormones
- Parathyroid Disorders and Treatments
- Neuroscience and Neuropharmacology Research
- Diabetes Treatment and Management
- Protein Kinase Regulation and GTPase Signaling
- Adipose Tissue and Metabolism
- Antibiotics Pharmacokinetics and Efficacy
- Bariatric Surgery and Outcomes
- Lipoproteins and Cardiovascular Health
- Metabolism, Diabetes, and Cancer
- Bone and Dental Protein Studies
- Renal function and acid-base balance
- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
University of St Andrews
2016-2025
St. Andrews University
2018-2021
Chinese Academy of Sciences
2018
In-Q-Tel
2018
Institute of Tibetan Plateau Research
2018
The Christie NHS Foundation Trust
2010
MRC Centre for Reproductive Health
2007-2009
The Queen's Medical Research Institute
2007-2009
Medical Research Council
2008-2009
Queen's Medical Centre
2008-2009
Albumin is the major transport protein in blood for Zn 2+ , a metal ion required physiological processes and recruited by various drugs toxins. However, -binding site(s) on albumin ill-defined. We have analyzed 18 x-ray crystal structures of human PDB identified potential five-coordinate site at interface domains I II consisting N ligands from His-67 His-247 O Asn-99, Asp-249, H 2 O, which are same amino acid as those zinc enzymes calcineurin, endonucleotidase, purple phosphatase. The...
Most blood plasma zinc is bound to albumin, but the structure of binding site has not been determined. Zn K-edge extended x-ray absorption fine spectroscopy and modeling studies show that major Zn(2+) on albumin a 5-coordinate with average Zn-O/N distances 1.98 A weak sixth O/N bond 2.48 A, consistent coordination His(67) Asn(99) from domain I, His(247) Asp(249) II (residues conserved in all sequenced mammalian albumins), plus water ligand. The dynamics I/II interface, thought be important...
Abstract Electron paramagnetic resonance (EPR) distance measurements are making increasingly important contributions to the studies of biomolecules by providing highly accurate geometric constraints. Combining double‐histidine motifs with Cu II spin labels can further increase precision measurements. It is also useful for proteins containing essential cysteines that interfere thiol‐specific labelling. However, non‐covalent coordination approach vulnerable low binding‐affinity. Herein,...
Human PHOSPHO1 is a phosphatase enzyme for which expression upregulated in mineralizing cells. This has been implicated the generation of Pi matrix mineralization, process central to skeletal development. member haloacid dehalogenase (HAD) superfamily Mg2+-dependent hydrolases. However, substrates are, as yet, unidentified and little known about its activity. We show here that exhibits high specific activities toward phosphoethanolamine (PEA) phosphocholine (PCho). Optimal enzymic activity...
Circulatory transport of the essential nutrient zinc primarily occurs through its binding to serum albumin. Here, we present first crystal structures mammalian albumins in complex with zinc. These structures, together accompanying data, allow identification key sites on human and equine albumins.
Aberrant Zn(2+) homeostasis is a hallmark of certain cardiomyopathies associated with altered contractile force. In this study, we addressed whether modulates cardiac ryanodine receptor gating and Ca(2+) dynamics in isolated cardiomyocytes. We reveal that high affinity regulator RyR2 displaying three modes operation. Picomolar free concentrations potentiate responses, but channel activation still dependent on the presence cytosolic Ca(2+). At >1 nm, main activating ligand, dependence...
Cys34 in domain I of the three‐domain serum protein albumin is binding site for a wide variety biologically and clinically important small molecules, provides antioxidant activity, constitutes largest portion free thiol blood. Analysis X‐ray structures reveals that loop containing Tyr84 occurs multiple conformations. In where well defined, there appears to be an H‐bond between OH sulfur Cys34. We show reaction 5,5′‐dithiobis(2‐nitrobenzoic acid) (DTNB) with Tyr84Phe mutant approximately four...
Effects of parathyroidectomy on parathyroid function and calcium (Ca) metabolism were carefully evaluated in 6 patients with primary hyperparathyroidism without symptoms normally attributed to the disease 7 bone or nephrolithiasis. Before parathyroidectomy, both groups demonstrated evidence sequelae hormone (PTH) excess, since they presented one more following features: low density by 125I-photon absorption, hypercalciuria (urinary Ca greater than 200 mg/day an intake 400 mg/day), negative...
Diabetes mellitus (DM) is a serious metabolic disorder, where impaired postprandial blood glucose regulation often leads to severe health complications. The natural chemical erythritol C4 polyol approved by the U.S. Food and Drug Administration for use as sweetener. Here, we examined potential role in control of levels DM. An anti-postprandial hyperglycemia effect upon administration (500 mg kg-1) was demonstrated alloxan-induced DM model mice monitoring changes after intragastric drugs...