5EI0

Structure of RCL-cleaved vaspin (serpinA12)

Summary for 5EI0

• Entry DOI: 10.2210/pdb5ei0/pdb
• Related: 4IF8 4Y3K 4Y40
• Descriptor: Serpin A12 (2 entities in total)
• Functional Keywords: serpin, cleaved, adipokine, hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: Q8IW75
• Total number of polymer chains: 2
• Total formula weight: 95073.62

Authors

Pippel, J.,Kuettner, B.E.,Ulbricht, D.,Daberger, J.,Schultz, S.,Heiker, J.T.,Strater, N. (deposition date: 2015-10-29, release date: 2015-11-11, Last modification date: 2024-01-10)

Primary citation

Pippel, J.,Kuettner, E.B.,Ulbricht, D.,Daberger, J.,Schultz, S.,Heiker, J.T.,Strater, N.
Crystal structure of cleaved vaspin (serpinA12).
Biol.Chem., 397:111-123, 2016

PubMed Abstract: The adipokine vaspin (serpinA12) is mainly expressed in white adipose tissue and exhibits various beneficial effects on obesity-related processes. Kallikrein 7 is the only known target protease of vaspin and is inhibited by the classical serpin inhibitory mechanism involving a cleavage of the reactive center loop between P1 (M378) and P1' (E379). Here, we present the X-ray structure of vaspin, cleaved between M378 and E379. We provide a comprehensive analysis of differences between the uncleaved and cleaved forms in the shutter, breach, and hinge regions with relation to common molecular features underlying the serpin inhibitory mode. Furthermore, we point out differences towards other serpins and provide novel data underlining the remarkable stability of vaspin. We speculate that the previously reported FKGx1Wx2x3 motif in the breach region may play a decisive role in determining the reactive center loop configuration in the native vaspin state and might contribute to the high thermostability of vaspin. Thus, this structure may provide a basis for future mutational studies.

PubMed: 26529565
DOI: 10.1515/hsz-2015-0229

Experimental method

X-RAY DIFFRACTION (2.5 Å)