Unraveling the Reaction between Heme (FeIV=O) Moiety and H2S
Unraveling the Reaction between Heme (FeIV=O) Moiety and H2S
批准号:
7625991
负责人:
JUAN LOPEZ-GARRIGA
金额:
$11.81万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
AchievementAffectAmino Acid SequenceAmino AcidsBacteriaBacterial InfectionsBehaviorBindingBinding SitesBiologicalBiophysicsBiopolymersBiotechnologyBloodBlood capillariesBooksCaliberCarbon MonoxideCationsCell AgingCellsCharacteristicsChemicalsChloride IonChloridesClamsComplementary DNAComplexConditionCoupledCrystallizationCyanidesDNA Sequence RearrangementDataData CollectionDatabasesDependenceDetectionDevelopmentDiffusionDiscriminationDisruptionDissociationDistalDoctor of PhilosophyEducationEducational CurriculumEducational process of instructingElectronicsEngineeringEnvironmentEnvironmental ExposureErythrocytesEscherichia coliFrequenciesGlobinGlucoseGlutamineGrantHemeHemeproteinsHeminHemoglobinHemoglobin JHumanHydrogen BondingHydrogen PeroxideHydrogen SulfideInorganic ChemistryInternationalInvestigationIsopropyl ThiogalactosideJournalsKineticsKnowledgeLaboratoriesLeadLengthLifeLigand BindingLigandsLiteratureLongitudinal StudiesLucina pectinata hemoglobin IManuscriptsMeasurementMethodologyMethodsModelingMolecularMolecular ConformationMolecular StructureMolecular WeightMonitorMovementMutateMutationMyoglobinNumbersObject AttachmentOxygenPeripheralPersonal SatisfactionPliabilityPopulationPorphyrinsPositioning AttributePreparationProceduresProductionPropertyProtein ChemistryProteinsProteomicsProtonsPublicationsPublished CommentPublishingPuerto RicoPumpPyrrolesRateReactionRecombinantsReportingResearchResearch Project GrantsResolutionRoentgen RaysRoleScienceScoreSepharoseSequence AlignmentSickle Cell AnemiaSiteSolutionsSolventsSpectroscopy, Fourier Transform InfraredStreamStructureStructure-Activity RelationshipStudentsSulfhemoglobinSulfidesSulfurSystemTechniquesThalassemiaTherapeuticTimeTrainingTyrosineUniversitiesUrsidae FamilyWorkX ray spectroscopyX-Ray Crystallographyabsorptionabstractingamino groupbasecapillarycarbonyl groupcell agechlorincomparativeconformerdimerexpression vectorflash photolysisfluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl etherhigh schoolimprovedinnovationmutantmyoglobin cyanidenanosecondprogramsprotein expressionreaction rateresearch studysensorsizestop flow techniquesulfhemesulfmyoglobinvibration
中文摘要
血红蛋白(Hb)和肌红蛋白(Mb)与过氧化氢(H2 O2)发生过氧化反应,
卟啉/r-阳离子自由基铁基化合物I(Fe ′ v =O Por*+)和铁基化合物II(Fe ′ v =O Por),
对红细胞非常敏感和有害。同时,硫化氢(H2S)进入血液
河流,通过环境暴露或细菌感染,可以与这些物种相互作用,导致
形成硫血红蛋白(sulfHb)和硫肌红蛋白(sulfMb),随后破坏Hb,
Mb函数。这些失活的蛋白质,其特定的血红素中间体和反应机制仍然是
未知,其特征在于具有在620 nm处的吸收带的血红素IX二氢卟酚衍生物
区域,带有饱和的4-乙烯基,H2S共价结合在该区域的<$-<$双键上,
吡咯C我们的最新数据表明,在相同的实验条件下,H2 O2和H2S,
来自Lucina pectinata的血红蛋白I、II和III(分别为Hbl和Hbll/Hbll 1)不形成这些血红蛋白。
硫血红素衍生物。Hbl递送H2S,而Hbll和Hblll将O2运输到共生细菌,尽管存在H2S。
在功能和化学结构上的多样性,在L.
栉蛤这种区别不被理解,将被用作理解
由于形成sulfHb 1和sulfHb 11/sulfHb 11应通过
通过与H2 O2和H2S反应产生的相同的高价血红素中间体,根据:
H2s
[Hbl(Fem)或Hbl(Fe”-O2)] + H2O2~-*(Fe 'v =O Por <$+)+(Felv=O Por)> SulfHbl(A)
化合物I化合物II
Hbl和Mb之间的另一个显著差异是铁基化合物I是Mb的近一千倍。
前者比后者更稳定。因此,我们的假设表明,硫血红素蛋白的机制,
形成可能取决于(1)血红素中心周围的氨基酸环境,(2)
铁基物种(化合物I和II)的寿命,以及(3)外围铁基物种的取向和结构。
血红素取代基为了探索这些替代方案,我们将监测648 nm、620 nm和419 nm的波段
通过UV-Vis和停止流动分别测定Hbl化合物I、sulfHbl和化合物II的nm特征,
在血红素蛋白(Mb、Hb 1、Hb 1突变体和Hb 11/Hb 111)的反应(A)后。中间和最后
结构将通过共振拉曼、NMR和X射线光谱学来追踪。数据将允许
评论(i)化合物I和II在人sulfHb和sulfMb形成中的作用,(ii)阐明
H2S的吡咯“C”反应的选择性,和(iii)有助于直接战略的发展
用于治疗和使sulfHb或sulfMb可逆为具有生物活性的人Hb和Mb。
英文摘要
The peroxidative reactions of hemoglobin (Hb) and myoglobin (Mb) with hydrogen peroxide (H2O2) produce
porphyrin /r-cation radical ferryl compound I (Fe'v=O Por*+) and ferryl compound II (Felv=O Por), which are
very reactive and detrimental to red cells. At the same time, hydrogen sulfide (H2S) entering the blood
stream, by environmental exposure or bacterial infections, can interact with these species leading to the
formation of sulfhemoglobin (sulfHb) and sulfmyoglobin (sulfMb) with the subsequent disruption of Hb and
Mb function. These inactive proteins, whose specific heme intermediates and reaction mechanism are still
unknown, are characterized by a protoheme IX chlorin derivative with an absorption band at the 620 nm
region, bearing the saturated 4-vinyl group with a H2S covalently bound across the¿-¿ double bond of the
pyrrole "C". Our latest data show that under the same experimental conditions, of H202 and H2S, the
hemoglobins I, II and III, (Hbl and Hbll/Hblll, respectively), from Lucina pectinata do not form these
sulfheme derivatives. Hbl delivers H2S, while Hbll and Hblll transport 02 to symbiotic bacteria, despite the
diversity in function and chemical structure no sulfheme-proteins derivatives have been detected in the L
pectinata clam. This discrimination is not understood and will be used as a model to comprehend the
mechanism toward sulfHb and sulfMb since the formation sulfHbl and sulfHbll/sulfHblll should proceed via
the same high valent heme intermediates generated by the reaction with H2O2and H2S according to:
H2S
[Hbl (Fem) or Hbl (Fe"-O2) ] + H2O2~-* (Fe'v=O Por¿+) + (Felv=O Por) > SulfHbl (A)
Compound I Compound II O2
Other notable difference between Hbl and Mb is that the ferryl compound I is near one thousand times
more stable in the former than in the latter. Thus, our hypothesis suggests that the mechanism of sulfhemeprotein
formation may depends on (1) the amino acid environment surrounding the heme center, (2)
the life time of the ferryl species (compound I and II), and (3) the orientation and structure of the peripheral
heme substituents. To explore these alternatives, we will monitor the bands at 648 nm, 620 nm, and 419
nm characteristic of Hbl compound I, sulfHbl, and compound II, respectively, by UV-Vis and stopped flow,
upon the reaction (A) of hemeproteins (Mb, Hbl, Hbl mutants, and Hbll/Hblll). The intermediate and final
structures will be pursued by resonance Raman, NMR and X-ray spectroscopy. The data will allow
commenting on (i) the role of compound I and II in the formation of human sulfHb and sulfMb, (ii) unravel
the selectivity of H2S for the pyrrole "C" reaction , and (iii) contribute to the development of direct strategies
for the treatment and reversibility of sulfHb or sulfMb to the biological active human Hb and Mb.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
RISE Enhancing Biomedical Sciences and Biomedical Engineering in Science and Tech
-
批准号:8528620
-
项目类别:
-
资助金额:$120.27万
-
财政年份:2010
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
RISE Enhancing Biomedical Sciences and Biomedical Engineering in Science and Tech
-
批准号:8306732
-
项目类别:
-
资助金额:$124.63万
-
财政年份:2010
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
RISE Enhancing Biomedical Sciences and Biomedical Engineering in Science and Tech
-
批准号:7935843
-
项目类别:
-
资助金额:$130.93万
-
财政年份:2010
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
RISE Enhancing Biomedical Sciences and Biomedical Engineering in Science and Tech
-
批准号:8118587
-
项目类别:
-
资助金额:$124.63万
-
财政年份:2010
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
Unraveling the Reaction between Heme (FeIV=O) Moiety and H2S
-
批准号:7284003
-
项目类别:
-
资助金额:$14.92万
-
财政年份:2007
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
UPR COBRE: PROTEIN STRUCTURE FUNCTION & DYNAMICS: ADMINISTRATIVE CORE
-
批准号:6981481
-
项目类别:
-
资助金额:$25.59万
-
财政年份:2004
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
H2S HEMOGLOBIN I STRUCTURE--SITE DIRECTED MUTAGENESIS STUDY
-
批准号:6591057
-
项目类别:
-
资助金额:$3.04万
-
财政年份:2002
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
CENTER FOR RESEARCH IN PROTEIN STRUCTURE, FUNCTION AND D
-
批准号:6530156
-
项目类别:
-
资助金额:$159.47万
-
财政年份:2001
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
CENTER FOR RESEARCH IN PROTEIN STRUCTURE, FUNCTION AND D
-
批准号:6411790
-
项目类别:
-
资助金额:$43.15万
-
财政年份:2001
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
H2S HEMOGLOBIN I STRUCTURE--SITE DIRECTED MUTAGENESIS STUDY
-
批准号:6449374
-
项目类别:
-
资助金额:$3.04万
-
财政年份:2001
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
CENTER FOR RESEARCH IN PROTEIN STRUCTURE, FUNCTION AND D
-
批准号:6654443
-
项目类别:
-
资助金额:$155.46万
-
财政年份:2001
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
CENTER FOR RESEARCH IN PROTEIN STRUCTURE, FUNCTION AND D
-
批准号:6569975
-
项目类别:
-
资助金额:$103.25万
-
财政年份:2001
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
H2S HEMOGLOBIN I STRUCTURE--SITE DIRECTED MUTAGENESIS STUDY
-
批准号:6311579
-
项目类别:
-
资助金额:$5.66万
-
财政年份:2000
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
H2S HEMOGLOBIN I STRUCTURE--SITE DIRECTED MUTAGENESIS STUDY
-
批准号:6347516
-
项目类别:
-
资助金额:$3.04万
-
财政年份:2000
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
H2S HEMOGLOBIN I STRUCTURE--SITE DIRECTED MUTAGENESIS STUDY
-
批准号:6107144
-
项目类别:
-
资助金额:$5.66万
-
财政年份:1999
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
HEME PROTEINS LIGAND DYNAMICS--THE CO POISON THRESHOLD
-
批准号:6271558
-
项目类别:
-
资助金额:$6.41万
-
财政年份:1998
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
HEME PROTEINS LIGAND DYNAMICS--THE CO POISON THRESHOLD
-
批准号:6240036
-
项目类别:
-
资助金额:$7.08万
-
财政年份:1997
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
HEME PROTEINS LIGAND DYNAMICS--THE CO POISON THRESHOLD
-
批准号:5211646
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:--
Unraveling the Reaction between Heme (FeIV=O) Moiety and H2S
-
批准号:8065496
-
项目类别:
-
资助金额:$11.26万
-
财政年份:--
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
HEME PROTEINS LIGAND DYNAMICS--THE CO POISON THRESHOLD
-
批准号:3734286
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:JUAN LOPEZ-GARRIGA
-
依托单位:
海外基金