000000372 001__ 372
000000372 005__ 20260302124420.0
000000372 0247_ $$2DOI$$a10.6083/M4SN06X3
000000372 037__ $$aETD
000000372 245__ $$aMechanistic studies of NO sensing and detoxificaton by bacterial iron-containing proteins
000000372 260__ $$bOregon Health and Science University
000000372 269__ $$a2009
000000372 336__ $$aDissertation
000000372 502__ $$bPh.D.
000000372 520__ $$aThis research investigates the molecular mechanisms by which metalloproteins detect and detoxify nitric oxide (NO). We characterized two bacterial NO‑sensor proteins that use distinct metal cofactors and examined the NO dioxygenase activity of hemoglobin homologues from mammals and bacteria, a key pathway for NO detoxification. A major focus was DevS, a heme‑based sensor kinase from Mycobacterium tuberculosis that responds to CO, NO, and hypoxia by activating the DevR regulon and promoting bacterial dormancy. Using UV–visible and resonance Raman spectroscopy along with activity assays of wild‑type and variant proteins, we identified a hydrogen‑bond network involving Tyr171 that enables DevS to distinguish activating ligands (CO and NO) from inhibitory O₂. Signal transmission to the kinase domain occurs through interactions between the heme‑binding GAF‑A domain and the adjacent GAF‑B domain. These findings advance understanding of NO sensing and detoxification across biological systems.
000000372 540__ $$fCC BY
000000372 542__ $$fIn copyright - single owner
000000372 650__ $$aNitric Oxide$$022931
000000372 650__ $$aSpectrum Analysis$$026223
000000372 650__ $$aMetalloproteins$$022108
000000372 650__ $$aBiochemical Phenomena$$015548
000000372 6531_ $$abioorganic chemistry
000000372 6531_ $$airon proteins
000000372 691__ $$aSchool of Medicine$$041369
000000372 692__ $$aDepartment of Science and Engineering$$041447
000000372 7001_ $$aYukl, Erik$$uOregon Health and Science University$$041354
000000372 7201_ $$aMoënne-Loccoz, Pierre$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor
000000372 8564_ $$948f7d0a5-3110-43d8-9728-d7fbbf69db16$$s22755745$$uhttps://digitalcollections.ohsu.edu/record/372/files/373_etd.pdf$$ePublic$$2ebe4d45f452356862660463cb369d09c$$31
000000372 905__ $$a/rest/prod/sb/39/78/28/sb397828k
000000372 909CO $$ooai:digitalcollections.ohsu.edu:372$$pstudent-work
000000372 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000372 980__ $$aTheses and Dissertations