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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1994-6-16
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pubmed:abstractText |
The reaction of alpha 2-macroglobulin (alpha 2M) with proteinases or methylamine causes a major conformational change in alpha 2M and cleavage of the alpha 2M thiol ester bonds. The resulting free Cys residues (Cys-949) contain the only free thiol groups in alpha 2M. In this investigation, we explored the role of Cys-949 in the binding of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 2 to alpha 2M-methylamine. Modification of preformed alpha 2M-methylamine with iodoacetamide did not change the binding affinity of alpha 2M-methylamine for TGF-beta 1 or TGF-beta 2; the apparent KD values were 82 nM and 10 nM, respectively. TGF-beta binding also remained unchanged when tested using an alpha 2M derivative prepared by simultaneous treatment of alpha 2M with methylamine and iodoacetamide. The slow thiol-disulfide exchange reaction that irreversibly stabilizes noncovalent growth factor-alpha 2M-methylamine complexes was completely inhibited by modification of Cys-949. These studies demonstrate that Cys-949 in alpha 2M is not essential for binding of TGF-beta 1 and TGF-beta 2 noncovalently; however, this residue plays a critical role in the covalent stabilization step of the reaction mechanism.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Iodoacetamide,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Macroglobulins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
200
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1578-85
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading | |
pubmed:year |
1994
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pubmed:articleTitle |
The role of cysteine-949 in the binding of transforming growth factor-beta 1 and transforming growth factor-beta 2 to alpha 2-macroglobulin.
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pubmed:affiliation |
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.
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