Unknown

Dataset Information

0

Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential.


ABSTRACT: Recombinant alkaline phosphatases are becoming promising protein therapeutics to prevent skeletal mineralization defects, inflammatory bowel diseases, and treat acute kidney injury. By substituting the flexible crown domain of human intestinal alkaline phosphatase (IAP) with that of the human placental isozyme (PLAP) we generated a chimeric enzyme (ChimAP) that retains the structural folding of IAP, but displays greatly increased stability, active site Zn²? binding, increased transphosphorylation, a higher turnover number and narrower substrate specificity, with comparable selectivity for bacterial lipopolysaccharide (LPS), than the parent IAP isozyme. ChimAP shows promise as a protein therapeutic for indications such as inflammatory bowel diseases, gut dysbioses and acute kidney injury.

SUBMITTER: Kiffer-Moreira T 

PROVIDER: S-EPMC3933536 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications

Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential.

Kiffer-Moreira Tina T   Sheen Campbell R CR   Gasque Kellen Cristina da Silva KC   Bolean Mayte M   Ciancaglini Pietro P   van Elsas Andrea A   Hoylaerts Marc F MF   Millán José Luis JL  

PloS one 20140224 2


Recombinant alkaline phosphatases are becoming promising protein therapeutics to prevent skeletal mineralization defects, inflammatory bowel diseases, and treat acute kidney injury. By substituting the flexible crown domain of human intestinal alkaline phosphatase (IAP) with that of the human placental isozyme (PLAP) we generated a chimeric enzyme (ChimAP) that retains the structural folding of IAP, but displays greatly increased stability, active site Zn²⁺ binding, increased transphosphorylatio  ...[more]

Similar Datasets

| S-EPMC3693508 | biostudies-literature
| S-EPMC1168075 | biostudies-other
| S-EPMC6351214 | biostudies-literature
| S-EPMC4824800 | biostudies-literature
| S-EPMC4062654 | biostudies-literature
| S-EPMC5743071 | biostudies-literature
| S-EPMC1270129 | biostudies-other
| S-EPMC1179117 | biostudies-other
| S-EPMC1137310 | biostudies-literature
| S-EPMC4136714 | biostudies-literature