Zn2+ stapling of N and C-terminal maintains stability and substrate affinity in GH26 endo-mannanase.
IR@CSIR-CFTRI
View Archive InfoField | Value | |
Relation |
http://ir.cftri.com/14388/
https://doi.org/10.1016/j.enzmictec.2019.109497 |
|
Title |
Zn2+ stapling of N and C-terminal maintains stability and substrate affinity in GH26 endo-mannanase.
|
|
Creator |
Gaurav Singh, Kaira
Usharani, D. Mukesh, Kapoor |
|
Subject |
07 Enzyme Biochemistry
|
|
Description |
Metal binding sites are present in one-third of proteins and are crucial for biological functions and structural maintenance. GH26 endo-mannanase (ManB-1601) from Bacillus sp. harbors a Zn2+ binding site which connects N (H1, H23) and C (E336)-terminal residues. Present study reveals how native circularization of ManB-1601 through Zn2+ coordination regulates the structure-function. We generated individual Zn2+ coordinating mutants and characterized them using biochemical and biophysical approaches. Contribution of individual Zn2+ coordination towards maintaining ManB-1601 stability and rigidity was in the following order H23>H1 > E336. Elimination of E336 and H23-Zn2+ coordination affected substrate hydrolysis to a greater degree than H1-Zn2+ coordination. Metal quantification of mutant proteins indicated that H23A did not contain Zn2+. Molecular dynamic simulation studies revealed disruption of H23-Zn2+ coordination leads to increased flexibility of N and C-terminal, active site loops and consequent drifting of substrate away from the active site region. Finally, mechanistic understanding on the functioning of Zn2+ site in ManB-1601 is developed wherein 1) H23 by anchoring Zn2+ ion majorly regulates the structure-function properties, 2) H1 provides thermostability, 3) E336 contributes towards maintaining substrate hydrolysis.
|
|
Date |
2020
|
|
Type |
Article
PeerReviewed |
|
Format |
pdf
|
|
Language |
en
|
|
Identifier |
http://ir.cftri.com/14388/1/Enzyme%20and%20Microbial%20Technology%202020.pdf
Gaurav Singh, Kaira and Usharani, D. and Mukesh, Kapoor (2020) Zn2+ stapling of N and C-terminal maintains stability and substrate affinity in GH26 endo-mannanase. Enzyme and Microbial Technology, 135. ISSN 0141-0229 |
|