Linked Life Data

15178254

Source:http://linkedlifedata.com/resource/pubmed/id/15178254

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-6-4
pubmed:databankReference
pubmed:abstractText
Multi-disciplinary studies of fluorescein-protein conjugates have led to the generation of a family of antibodies with common idiotypes and affinities for fluorescein ranging over five orders of magnitude. The high affinity 4-4-20 prototype traps the ligand in a highly complementary binding slot, which is lined by multiple aromatic side-chains. An antibody (9-40) of intermediate affinity belongs to the same idiotypic family as 4-4-20 and shares substantial amino acid identities within the VL and VH domains. To establish the structural basis for the affinity differences, we solved the crystal structure of the 9-40 Fab-fluorescein complex at a resolution of 2.3A. Similar to 4-4-20, 9-40 binds fluorescein in a tight aromatic slot with its xanthenonyl ring system accommodated by end-on insertion. However, the combined effects of the amino acid substitutions have resulted in reorganization of the binding site, with the HCDR3 loops showing the greatest differences in conformations. Access to the binding site of 9-40 is substantially more open, leaving the fluorescein's phenylcarboxylate moiety partially exposed to solvent. In addition to the usage of a different D (diversity) mini-gene encoding the HCDR3 loop, the decrease in fluorescein affinity in the 9-40 antibody family appears to be correlated with the substitution of histidine (9-40) for arginine (4-4-20) in position 34 of the antibody light chains.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1141-51
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Three-dimensional structures of idiotypically related Fabs with intermediate and high affinity for fluorescein.
pubmed:affiliation
Crystallography Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't