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HuCal VLk 2 Problem Spots

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CDRs VL
positive Phi angles
cis/trans Pro residues
H-Bonds
V/C interf. VL
Core residues VL
Dimer interf. VL Haptens
Dimer interf. VL Oligom.
Dimer interf. VL Proteins
Antigen interf. VL Haptens
Antigen interf. VL Oligom.
Antigen interf. VL Proteins
Randomized residues VL lambda
Randomized residues VL kappa
L3: Val->Ser
exposed hydrophobic side chain, no stabilizing contacts.
L9: Leu->Ser
exposed hydrophobic side chain, no stabilizing contacts.
In 4/4/20, the combination of L9 Leu->Ser with L15 Leu->Ser brought no improvement. In Rei, Ala L15->Leu was found to be strongly stabilizing, therefore L15 Leu->Ser probably destabilized 4/4/20 and masked any possible improvement through L9 Leu->Ser (beneficial in His)
L15: Pro->Leu
exposed hydrophobic side chain,
In Rei, L15 Ala->Leu was found to be strongly stabilizing(-7.0kJ/mol), L15 Ala->Pro somewhat less so (-4.5kJ/mol), therefore a stabilizing effect of Pro->Leu could be expected.
Leu->Glu was found to have a negative effect in 4/4/20
No data on how this affects FAB format
L45: Leu->Gln
Charge cluster
Buried, but the quite strongly conserved Gln, forms hydrogen bonds to the conserved buried charge cluster involving L77 Arg, L99 Glu and L100 Asp. In VH, H45 contains a strongly conserved Arg. The effect of this position has not been experimentaly tested yet, but may be done in the near future (His)
L53: Gln->Lys
Charge cluster, mostly Lys , Arg in VK2
4T5: Thr->Lys improved production
L58: Leu positive phi angle
L95: Arg->Ser 4T3 Thr->Ser positive effect on production, His: positive effect
L101:Val-> Thr
exposed hydrophobic side chain,
4T5: Leu->Ala pos. effect on production 4D5Flu: F selected over ASTIV, Hag: L101 Leu->Gln strongly selected, but potentially stabilizing lateral interaction with Pro L15 and Ile L147
No data on how this affects FAB format
L103:Val->Thr
exposed hydrophobic side chain,
should not affect FAB
L147: Ile->Thr
exposed hydrophobic side chain,but potentially stabilizing lateral interaction with Pro L15 and Val L101
No data on how this affects FAB format

HuCal Structure Display VLk 2

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AAAAA Homepage Zürich University Dept. of Biochemistry Plückthun Group Annemarie Honegger

Last Modified by A.Honegger Tuesday, March 25, 2008