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The prosegment–subtilisin BPN′ complex: crystal structure of a specific ‘foldase’
- Source :
- Structure. 3:907-914
- Publication Year :
- 1995
- Publisher :
- Elsevier BV, 1995.
-
Abstract
- Background: The folding of the bacterial protease subtilisin BPN′ (SBT) is dependent on its 77-residue prosegment, which is then autocatalytically removed to give the mature enzyme. Mature subtilisin represents a class of proteins that lacks an efficient folding pathway. Refolding of mature SBT is extremely slow unless catalyzed by the independently expressed prosegment, leading to a bimolecular complex. Results We report the crystal structure at 2.0 a resolution of the prosegment–SBT complex and consider its implications for prosubtilisin BPN′ maturation and folding catalysis. The prosegment forms a compact domain that binds SBT through an extensive interface involving the enzyme's two parallel surface helices (residues 104–116 and 133–144), supplying negatively charged caps to the N termini of these helices. The prosegment C terminus binds in the enzyme active site in a product-like manner, with Tyr77 in the P1 binding pocket. Conclusion The structure of the complex supports a unimolecular mechanism for prosubtilisin cleavage, involving a 25 a rearrangement of the SBT N terminus in a late folding step. A mechanism of folding catalysis in which the two helices and their connecting β strand form a prosegment-stabilized folding nucleus is proposed. While this putative nucleus is stabilized by prosegment binding, the N-terminal and C-terminal subdomains of SBT could fold by propagation.
- Subjects :
- Models, Molecular
chaperonin
Enzyme Precursors
Protein Folding
biology
Protein Conformation
Chemistry
Stereochemistry
C-terminus
Subtilisin
Active site
X-ray crystal structure
Crystallography, X-Ray
Peptide Fragments
subtilisin BPN′
Chaperonin
N-terminus
prosegment
Protein structure
Structural Biology
Foldase
biology.protein
Protein folding
Subtilisins
Molecular Biology
Subjects
Details
- ISSN :
- 09692126
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Structure
- Accession number :
- edsair.doi.dedup.....98b3b7d36a35fcd8fd69915433d506f5