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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1988-12-28
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pubmed:abstractText |
The binding to carboxypeptidase A of two phosphonic acid analogues of 2-benzylsuccinate, 2-DL-2-benzyl-3-phosphonopropionic acid (inhibitor I) and 2-DL-2-benzyl-3-(-O-ethylphosphono)propionic acid (inhibitor II) was studied by observing their 31P resonances when free and bound to the enzyme in the range of pH from 5 to 10. The binding of I by co-ordination to the active-site Zn(II) lowered the highest pKa of I from a value of 7.66(+/- 0.10) to a value of 6.71(+/- 0.17). No titration of any protons on II occurred over the pH range studied. The enzyme-bound inhibitor II also did not titrate over the pH range 6.17-7.60. The pH-dependencies of the apparent inhibition constants for I and II were also investigated by using N-(-2-(furanacryloyl)-L-phenylalanyl-L-phenylalanine as substrate. Two enzymic functional groups with pKa values of 5.90(+/- 0.06) and 9.79(+/- 0.14) must be protonated for binding of inhibitor I, and two groups with pKa values of 6.29(+/- 0.10) and 9.19(+/- 0.15) for binding of inhibitor II. Over the pH range from 6.71 to 7.66, inhibitor I binds to the enzyme in a complex of the enzyme in a more protonated form, and the inhibitor in a less protonated form than the predominant unligated forms at this pH. Mock & Tsay [(1986) Biochemistry 25, 2920-2927] made a similar finding for the binding of L-2-(1-carboxy-2-phenylethyl)-4-phenylazophenol over a pH range of nearly 4 units. The true inhibition constant for the dianionic form of inhibitor I (racemic) was calculated to be 54.0(+/- 5.9) nM and that of the trianionic form to be 5.92(+/- 0.65) nM. The true inhibition constant of the fully ionized II (racemic) was calculated to be 79.8(+/- 6.4) nM.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-14069557,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-200262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-210041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-33168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-3427026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-3718930,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-3782076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-3840231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-3863130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-4084224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-41155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-427123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-4735879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-5241536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-5529708,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-5682314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-5719196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-6364704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-6946483,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3196297-7138846
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
254
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
847-53
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
1988
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pubmed:articleTitle |
Ionization states of the complex formed between 2-benzyl-3-phosphonopropionic acid and carboxypeptidase A.
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pubmed:affiliation |
Department of Biochemistry, University of Kentucky, Lexington 40536.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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