Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential.
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 placen...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089374&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850024055448535040 |
|---|---|
| author | Tina Kiffer-Moreira Campbell R Sheen Kellen Cristina da Silva Gasque Mayte Bolean Pietro Ciancaglini Andrea van Elsas Marc F Hoylaerts José Luis Millán |
| author_facet | Tina Kiffer-Moreira Campbell R Sheen Kellen Cristina da Silva Gasque Mayte Bolean Pietro Ciancaglini Andrea van Elsas Marc F Hoylaerts José Luis Millán |
| author_sort | Tina Kiffer-Moreira |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-513a6df17a5e41f89f2e9d3e5e6a4d61 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-513a6df17a5e41f89f2e9d3e5e6a4d612025-08-20T03:01:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8937410.1371/journal.pone.0089374Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential.Tina Kiffer-MoreiraCampbell R SheenKellen Cristina da Silva GasqueMayte BoleanPietro CiancagliniAndrea van ElsasMarc F HoylaertsJosé Luis MillánRecombinant 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089374&type=printable |
| spellingShingle | Tina Kiffer-Moreira Campbell R Sheen Kellen Cristina da Silva Gasque Mayte Bolean Pietro Ciancaglini Andrea van Elsas Marc F Hoylaerts José Luis Millán Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. PLoS ONE |
| title | Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. |
| title_full | Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. |
| title_fullStr | Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. |
| title_full_unstemmed | Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. |
| title_short | Catalytic signature of a heat-stable, chimeric human alkaline phosphatase with therapeutic potential. |
| title_sort | catalytic signature of a heat stable chimeric human alkaline phosphatase with therapeutic potential |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089374&type=printable |
| work_keys_str_mv | AT tinakiffermoreira catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT campbellrsheen catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT kellencristinadasilvagasque catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT maytebolean catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT pietrociancaglini catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT andreavanelsas catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT marcfhoylaerts catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential AT joseluismillan catalyticsignatureofaheatstablechimerichumanalkalinephosphatasewiththerapeuticpotential |