Characterizing the structure of alkane hydroxylase (ALKB) and related Diiron Enzymes
Characterizing the structure of alkane hydroxylase (ALKB) and related Diiron Enzymes
批准号:
9092672
负责人:
RACHEL Narehood AUSTIN
金额:
$22.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2005
资助国家:
美国
项目状态:
已结题
起止时间:
2005-03-01 至 2018-03-31
中文摘要
项目总结
英文摘要
Project Summary
Bacteria readily oxidize alkanes utilizing the metalloenzyme alkane hydroxylase (AlkB) and thus the actions of
AlkB represent one of nature’s best defenses against the environmental effects of oil spills. Mammalian fatty
acids are also desaturated by integral membrane fatty acid desaturases that are structurally quite similar to AlkB.
It is not understood why AlkB catalyzes the addition of an OH group to an alkane while desaturases convert
single C-C bonds to double C=C bonds. AlkB and soluble methane monooxygenase (sMMO) both catalyze the
transformation of inert C-H bonds using a diiron catalyst but AlkB has a diiron catalyst with primarily nitrogen
atoms as ligands while sMMO has an oxygen-rich coordination site. The coordination environment is predicted
to influence the electronic structure and hence reactivity but the electronic structure of AlkB has not been
characterized. The long-term objective of this research effort is to understand how the structure of AlkB
determines the chemistry it affects and to use this knowledge to deepen our understanding of how biology
selectively activates molecular oxygen and catalyzes the oxidation of inert hydrocarbons. An associated
objective is to understand how structurally very similar biological motifs select between catalyzing the
hydroxylation of alkanes or their desaturation. The primary goal of the specific research proposed is obtain a
well-diffracting crystal of AlkB that will enable us to determine the three-dimensional structure of this enzyme.
Related goals are to spectroscopically characterize the ground state and reactive intermediates and to begin
explore AlkBs and related metalloenzymes from additional microorganisms. These goals enable us to test the
hypothesis that the structures of the active sites of all AlkBs and membrane-spanning desaturases are the same
but that structural differences in the substrate binding pocket control substrate selectivity and catalyst reactivity.
If successful, this work would have an impact on bioinorganic chemistry and environmental chemistry. A three-
dimensional structure of AlkB would help to answer many questions about the range of chemical motifs that
biology can use to oxidize alkanes. It would also answer questions about some of the chemical processes
utilized in the environmental response to oil spills.
期刊论文(8)
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Metals in marine biochemistry.
海洋生物化学中的金属。
DOI:
10.1039/c4mt90017k
发表时间:
2014
期刊:
Metallomics : integrated biometal science
影响因子:
--
作者:
[Austin,RachelNarehood, Saito,MakA]
通讯作者:
Saito,MakA
DOI:
10.3389/fmicb.2013.00109
发表时间:
2013
期刊:
Frontiers in microbiology
影响因子:
5.2
作者:
[Bertrand EM, Keddis R, Groves JT, Vetriani C, Austin RN]
通讯作者:
Austin RN
DOI:
10.3389/fmicb.2013.00338
发表时间:
2013
期刊:
Frontiers in microbiology
影响因子:
5.2
作者:
[Austin RN, Callaghan AV]
通讯作者:
Callaghan AV
DOI:
10.1021/ja3059149
发表时间:
2012-12-19
期刊:
Journal of the American Chemical Society
影响因子:
15
作者:
[Cooper HL, Mishra G, Huang X, Pender-Cudlip M, Austin RN, Shanklin J, Groves JT]
通讯作者:
Groves JT
DOI:
10.1021/acs.biochem.7b00338
发表时间:
2017-07-05
期刊:
Biochemistry
影响因子:
2.9
作者:
[Hsieh CH, Huang X, Amaya JA, Rutland CD, Keys CL, Groves JT, Austin RN, Makris TM]
通讯作者:
Makris TM
Molecular mechanisms of alkane hydroxylase (AlkB) reactivity and selectivity
-
批准号:10671699
-
项目类别:
-
资助金额:$29.27万
-
财政年份:2020
-
负责人:RACHEL Narehood AUSTIN
-
依托单位:
Molecular mechanisms of alkane hydroxylase (AlkB) reactivity and selectivity
-
批准号:10259889
-
项目类别:
-
资助金额:$29.01万
-
财政年份:2020
-
负责人:RACHEL Narehood AUSTIN
-
依托单位:
Molecular mechanisms of alkane hydroxylase (AlkB) reactivity and selectivity
-
批准号:10451683
-
项目类别:
-
资助金额:$29.17万
-
财政年份:2020
-
负责人:RACHEL Narehood AUSTIN
-
依托单位:
Characterizing the structure of alkane hydroxylase (AlkB) and related diiron enzy
-
批准号:8573915
-
项目类别:
-
资助金额:$9.63万
-
财政年份:2005
-
负责人:RACHEL Narehood AUSTIN
-
依托单位:
Characterizing hydroxylation mechanism of diiron enzymes
-
批准号:6847374
-
项目类别:
-
资助金额:$20.87万
-
财政年份:2005
-
负责人:RACHEL Narehood AUSTIN
-
依托单位:
国内基金
海外基金
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