Processivity and Catalytic Mechanism of Aldosterone Synthase
Processivity and Catalytic Mechanism of Aldosterone Synthase
醛固酮合酶的持续合成能力和催化机制
批准号：
10600520
负责人：
Juan Jose Valentin-Goyco
金额：
$4.01万
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
项目状态：
未结题
起止时间：
2023-01-05 至 2025-01-04
关键词：
AdrenodoxinAdverse effectsAffectAldosteroneAmino AcidsAnalytical ChemistryAryl Hydrocarbon HydroxylasesBindingBiological AssayCYP11B2 geneCardiovascular systemCellsCellular AssayCessation of lifeCholesterolClinical ResearchComplexCorticosteroneCortodoxoneCoupledCytochrome P450DeoxycorticosteroneDevicesDiseaseDissociationDrug DesignEmbryoEnhancersEnzyme KineticsEnzymesEventFerredoxin-NADP ReductaseFunctional disorderHeart failureHomeostasisHormonesHydrocortisoneHydroxylationHyperaldosteronismHypertensionImpairmentIn VitroIncidenceInner mitochondrial membraneIsoenzymesKidney FailureKineticsKnowledgeLengthMass Spectrum AnalysisMineralocorticoid ReceptorMineralocorticoidsMitochondriaMonitorMutationMyocardial InfarctionOperative Surgical ProceduresOxidasesOxidation-ReductionPatientsPhospholipidsPhysiologic pulsePlaguePoint MutationProductionPropertyPublishingRare DiseasesRattusReactionRenin-Angiotensin SystemResearchRoleSecondary HypertensionSodiumSpironolactoneSteroid biosynthesisStrokeStructureTachycardiaTestingTherapeuticWaterantagonistblood pressure controlblood pressure regulationcrosslinkdrug developmentexperimental studyheart cellhigh riskinhibitornanodiskoxidationprotein expressionreconstitutionside effectstandard of caresteroidogenic acute regulatory proteintherapy design
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Abstract
The finely tuned production of aldosterone controls blood pressure by regulating water and sodium retention.
The overproduction of aldosterone, however, leads to primary aldosteronism, the major form of secondary
hypertension. This mineralocorticoid hormone is produced by cytochrome P450 11B2 (CYP11B2), also known
as aldosterone synthase. While lowering aldosterone levels through inhibition of CYP11B2 has been established
as a potential therapeutic approach, a few challenges are associated with this tactic. For example, CYP11B2
shares a 93% sequence identity with the cortisol-producing P450 11B1 (CYP11B1). Despite the similarities
between CYP11B1 and CYP11B2, there exist key functional and structural differences. Overall, this research
aims to understand how these subtle differences contribute to the catalytic function of these enzymes in order to
aid drug development.
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