1MKK

Disulfide deficient mutant of vascular endothelial growth factor A (C61A and C104A)

1MKK の概要

• エントリーDOI: 10.2210/pdb1mkk/pdb
• 関連するPDBエントリー: 1MJV 1MKG 2VPF
• 分子名称: Vascular Endothelial Growth Factor A (2 entities in total)
• 機能のキーワード: cystine-knot growth factor, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted : P15692
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22391.93

構造登録者

Muller, Y.A.,Heiring, C.,Misselwitz, R.,Welfle, K.,Welfle, H. (登録日: 2002-08-29, 公開日: 2002-12-11, 最終更新日: 2024-11-20)

主引用文献

Muller, Y.A.,Heiring, C.,Misselwitz, R.,Welfle, K.,Welfle, H.
The cystine knot promotes folding and not thermodynamic stability in vascular endothelial growth factor
J.Biol.Chem., 277:43410-43416, 2002

PubMed Abstract: Cystine knots consist of three intertwined disulfide bridges and are considered major determinants of protein stability in proteins in which they occur. We questioned this function and observed that removal of individual disulfide bridges in human vascular endothelial growth factor (VEGF) does not reduce its thermodynamic stability but reduces its unexpected high thermal stability of 108 degrees C by up to 40 degrees C. In wild-type VEGF (deltaG(u,25)(0) = 5.1 kcal.mol(-1)), the knot is responsible for a large entropic stabilization of TdeltaS(u,25)(0) = -39.3 kcal mol(-1), which is compensated for by a deltaH(u,25)(0) of -34.2 kcal mol(-1). In the disulfide-deficient mutants, this entropic stabilization disappears, but instead of a decrease, we observe an increase in the thermodynamic stability by about 2 kcal.mol(-1). A detailed crystallographic analysis of the mutant structures suggests a role of the cystine knot motif in protein folding rather than in the stabilization of the folded state. When assuming that the sequential order of the disulfide bridge formation is conserved between VEGF and glycoprotein alpha-subunit, the crystal structure of the mutant C61A-C104A, which deviates by a root mean square deviation of more than 2.2 A from wild-type VEGF, identifies a true folding intermediate of VEGF.

PubMed: 12207021
DOI: 10.1074/jbc.M206438200

実験手法

X-RAY DIFFRACTION (1.32 Å)