BACKGROUND Tissue engineering and bone substitutes are subjects of intensive ongoing research. If the healing of bone fractures is delayed, osteoinductive materials that induce mesenchymal stem cells (MSCs) to form bone are necessary. The use of Bone Morphogenetic Protein - 2 is a common means to enhance effectiveness and accelerate the healing process. A delivery system that maintains and rele...

The nucleotide phosphodiesterase/pyrophosphatase from Xanthomonas axonopodis (NPP) is a structural and evolutionary relative of alkaline phosphatase that preferentially hydrolyzes phosphate diesters. With the goal of understanding how these two enzymes with nearly identical Zn2+ bimetallo sites achieve high selectivity for hydrolysis of either phosphate monoesters or diesters, we have measured ...

Enzymes capable of benzoate ester hydrolysis have several potential medical and industrial applications. A variant of human carbonic anhydrase II (HCAII) was constructed, by rational design, that is capable of hydrolysing para-nitrophenyl benzoate (pNPBenzo) with an efficiency comparable to some naturally occuring esterases. The design was based on a previously developed strategy, [G. Höst, L.G...

Bacteriophage λ phosphoprotein phosphatase (λPP) has structural similarity to the mammalian Ser/Thr phosphoprotein phosphatases (PPPs) including the immunosuppressant drug target calcineurin. PPPs possess a conserved active site containing a dinuclear metal cluster, with metal ligands provided by a phosphoesterase motif plus two additional histidine residues at the C-terminus. Multiple sequence...

INTRODUCTION: Staphylococcus aureus is the major causative pathogen in osteomyelitis, responsible for approximately 50% of all cases. In some cases, S. aureus can internalize into non-phagocytic mammalian cells to allow persistent infection. Others have measured internalized bacteria after removal of non-internalized bacteria by a 2 hour treatment in gentamicin. Based on our knowledge of adhere...

In the United States nearly 20 million people have osteoarthritis, a disease which is characterized by the degeneration of joints, including bone and cartilage. As a result, back pain is the second leading cause of sick leave. Further, osteoporotic fractures have doubled in the last decade, and 40% of all women over the age of 50 will suffer from an osteoporotic-related fracture in their life-t...

Introduction: Adipose-derived mesenchymal cells (AMCs) are a promising cell source for orthopaedic tissue engineering applications due to their accessibility and multi-lineage potential. However, future use in bone and cartilage regeneration requires development of successful strategies for driving AMCs to osteogenic and chondrogenic lineages. Recent work has demonstrated that bone morphogeneti...

Bacteriophage λ protein phosphatase (λPP) is a member of a large family of metal-containing phosphoesterases, including purple acid phosphatase, protein serine/threonine phosphatases, 5′-nucleotidase, and DNA repair enzymes such as Mre11. λPP can be activated several-fold by various divalent metal ions, with Mn2+ and Ni2+ providing the most significant activation. Despite the extensive characte...

Bacteriophage λ protein phosphatase (λPP) with Mn2+ as the activating metal cofactor was studied using phosphatase inhibition kinetics and electron paramagnetic resonance (EPR) spectroscopy. Orthophosphate and the oxoanion analogues orthovanadate, tungstate, molybdate, arsenate, and sulfate were shown to inhibit the phosphomonoesterase activity of λPP, albeit with inhibition constants (Ki) that...