Linked Life Data

2730566

Source:http://linkedlifedata.com/resource/pubmed/id/2730566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1989-6-27
pubmed:abstractText
1. 2-(N'-Acetyl-L-phenylalanyl)hydroxyethyl 2'-pyridyl disulphide (compound V) was synthesized, and a study of the pH-dependence of the second-order rate constant (k) for its reaction with the catalytic-site thiol group of papain (EC 3.4.22.2) was used to evaluate the consequences for transition-state geometry of the presence of a hydrophobic occupant for the S2 subsite of the enzyme in the absence of the N-H component of the P1-P2 amide bond. 2. Comparison of the pH-dependences of K for reactions of compound (V), 2-(acetamido)ethyl 2'-pyridyl disulphide (compound I) and 2-(acetoxy)ethyl 2'-pyridyl disulphide (compound III) with the cysteine-proteinase minimal catalytic-site model, benzimidazol-2-ylmethanethiol, established the activation of all of these pyridyl disulphides by hydronation and that their reactivities are relatively insensitive to structural change in the non-pyridyl part of the molecule. The marked differences in their reactivities towards papain therefore derive from binding, either directly, or indirectly via signalling mechanisms. 3. Comparison of the kinetic data for the reaction of papain with compound (V) with those for analogous reactions with reactivity probes that provide opportunities for a variety of binding interactions in the S1-S2 intersubsite region and in the S2 subsite itself lead to the following conclusions: (a) the (Gly-66) N-H...O = C less than (P1-P2 ester) interaction of papain with compound (III) provides for better binding relative to that for a probe with a simple hydrocarbon side chain, but no signalling to the catalytic site to provide a (His-159)-ImH+-assisted transition state; (b) when this interaction is augmented either by a (P1-P2 amide) N-H...O = C less than (Asp-158) interaction (compound I) or hydrophobic P2/S2 contacts (compound V), signalling to the catalytic region occurs to provide the assisted transition state; (c) when both the P2/S2 contacts and the interaction involving Gly-66 exist, provision additionally of the (P1-P2 amide) N-H...O = C less than (Asp-158) interaction [as in 2-(N'-acetyl-L-phenylalanylamino)ethyl 2'-pyridyl disulphide] serves only to assist the binding without an additional signalling effect. 4. Such studies promise to allow binding interactions that merely locate substrates in appropriate enzyme loci to be distinguished from those that transmit signals with a chemical consequence to catalytic sites.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-16744552, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-17835820, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-234862, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-27512, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-2825655, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-2839145, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3168, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3223929, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3296192, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3481264, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3518794, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3547407, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3663111, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3838593, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-3865201, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-435250, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-4399049, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-4692655, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-4721623, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-5084800, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-5126466, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-518556, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-6309137, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-687376, http://linkedlifedata.com/resource/pubmed/commentcorrection/2730566-7025834
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
258
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
755-64
pubmed:dateRevised
2010-9-9
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Identification of signalling and non-signalling binding contributions to enzyme reactivity. Alternative combinations of binding interactions provide for change in transition-state geometry in reactions of papain.
pubmed:affiliation
Department of Biochemistry, St. Bartholomew's Hospital Medical College, University of London, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't