2JB5

Fab fragment in complex with small molecule hapten, crystal form-1

Summary for 2JB5

• Entry DOI: 10.2210/pdb2jb5/pdb
• Related: 2C0V 2JB6
• Descriptor: FAB FRAGMENT MOR03268 HEAVY CHAIN, FAB FRAGMENT MOR03268 LIGHT CHAIN, 2-{(1E,3Z,5E,7E)-7-[3,3-DIMETHYL-5-SULFO-1-(2-SULFOETHYL)-1,3-DIHYDRO-2H-INDOL-2-YLIDENE]-4-METHYLHEPTA-1,3,5-TRIEN-1-YL}-3,3-DIMETHYL-5-SULFO-1-(2-SULFOETHYL)-3H-INDOLIUM, ... (4 entities in total)
• Functional Keywords: cdr, tsc, fab, hucal, fluorescent dye, immunoglobulin domain, antibody fragment, diagnostic imaging, immune system
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 49855.20

Authors

Hillig, R.C.,Baesler, S.,Malawski, G.,Badock, V.,Bahr, I.,Schirner, M.,Licha, K. (deposition date: 2006-12-03, release date: 2008-01-08, Last modification date: 2024-10-23)

Primary citation

Hillig, R.C.,Urlinger, S.,Fanghanel, J.,Brocks, B.,Haenel, C.,Stark, Y.,Sulzle, D.,Svergun, D.I.,Baesler, S.,Malawski, G.,Moosmayer, D.,Menrad, A.,Schirner, M.,Licha, K.
Fab Mor03268 Triggers Absorption Shift of a Diagnostic Dye Via Packaging in a Solvent-Shielded Fab Dimer Interface
J.Mol.Biol., 377:206-, 2008

PubMed Abstract: Molecular interactions between near-IR fluorescent probes and specific antibodies may be exploited to generate novel smart probes for diagnostic imaging. Using a new phage display technology, we developed such antibody Fab fragments with subnanomolar binding affinity for tetrasulfocyanine, a near-IR in vivo imaging agent. Unexpectedly, some Fabs induced redshifts of the dye absorption peak of up to 44 nm. This is the largest shift reported for a biological system so far. Crystal structure determination and absorption spectroscopy in the crystal in combination with microcalorimetry and small-angle X-ray scattering in solution revealed that the redshift is triggered by formation of a Fab dimer, with tetrasulfocyanine being buried in a fully closed protein cavity within the dimer interface. The derived principle of shifting the absorption peak of a symmetric dye via packaging within a Fab dimer interface may be transferred to other diagnostic fluorophores, opening the way towards smart imaging probes that change their wavelength upon interaction with an antibody.

PubMed: 18241888
DOI: 10.1016/J.JMB.2007.12.071

Experimental method

X-RAY DIFFRACTION (2.8 Å)