Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites.
The most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite's ability to infect the host's liver, but its role during parasite growth inside erythrocytes, the stage responsible for symptoma...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3383692?pdf=render |
| _version_ | 1818421766544949248 |
|---|---|
| author | Eric Salazar Erin M Bank Nicole Ramsey Kenneth C Hess Kirk W Deitsch Lonny R Levin Jochen Buck |
| author_facet | Eric Salazar Erin M Bank Nicole Ramsey Kenneth C Hess Kirk W Deitsch Lonny R Levin Jochen Buck |
| author_sort | Eric Salazar |
| collection | DOAJ |
| description | The most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite's ability to infect the host's liver, but its role during parasite growth inside erythrocytes, the stage responsible for symptomatic malaria, is less clear. The P. falciparum genome encodes two adenylyl cyclases, the enzymes that synthesize cAMP, PfACα and PfACβ. We now show that one of these, PfACβ, plays an important role during the erythrocytic stage of the P. falciparum life cycle. Biochemical characterization of PfACβ revealed a marked pH dependence, and sensitivity to a number of small molecule inhibitors. These inhibitors kill parasites growing inside red blood cells. One particular inhibitor is selective for PfACβ relative to its human ortholog, soluble adenylyl cyclase (sAC); thus, PfACβ represents a potential target for development of safe and effective antimalarial therapeutics. |
| first_indexed | 2024-12-14T13:15:35Z |
| format | Article |
| id | doaj.art-a51189cb507b46b4904d2127662aa690 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T13:15:35Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a51189cb507b46b4904d2127662aa6902022-12-21T23:00:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3976910.1371/journal.pone.0039769Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites.Eric SalazarErin M BankNicole RamseyKenneth C HessKirk W DeitschLonny R LevinJochen BuckThe most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite's ability to infect the host's liver, but its role during parasite growth inside erythrocytes, the stage responsible for symptomatic malaria, is less clear. The P. falciparum genome encodes two adenylyl cyclases, the enzymes that synthesize cAMP, PfACα and PfACβ. We now show that one of these, PfACβ, plays an important role during the erythrocytic stage of the P. falciparum life cycle. Biochemical characterization of PfACβ revealed a marked pH dependence, and sensitivity to a number of small molecule inhibitors. These inhibitors kill parasites growing inside red blood cells. One particular inhibitor is selective for PfACβ relative to its human ortholog, soluble adenylyl cyclase (sAC); thus, PfACβ represents a potential target for development of safe and effective antimalarial therapeutics.http://europepmc.org/articles/PMC3383692?pdf=render |
| spellingShingle | Eric Salazar Erin M Bank Nicole Ramsey Kenneth C Hess Kirk W Deitsch Lonny R Levin Jochen Buck Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. PLoS ONE |
| title | Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. |
| title_full | Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. |
| title_fullStr | Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. |
| title_full_unstemmed | Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. |
| title_short | Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. |
| title_sort | characterization of plasmodium falciparum adenylyl cyclase β and its role in erythrocytic stage parasites |
| url | http://europepmc.org/articles/PMC3383692?pdf=render |
| work_keys_str_mv | AT ericsalazar characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites AT erinmbank characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites AT nicoleramsey characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites AT kennethchess characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites AT kirkwdeitsch characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites AT lonnyrlevin characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites AT jochenbuck characterizationofplasmodiumfalciparumadenylylcyclasebanditsroleinerythrocyticstageparasites |