Structural Catalytic Core of the Members of the Superfamily of Acid Proteases

Alexandre Denesyuk; Konstantin Denessiouk; Mark Johnson; Vladimir Uversky

doi:10.3390/molecules29153451

Structural Catalytic Core of the Members of the Superfamily of Acid Proteases

Alexandre Denesyuk^*
, Konstantin Denessiouk
, Mark Johnson
, Vladimir Uversky^*

^*Corresponding author for this work

Research output: Contribution to journal › Review Article or Literature Review › peer-review

2 Citations (Scopus)

134 Downloads (Pure)

Abstract

The superfamily of acid proteases has two catalytic aspartates for proteolysis of their peptide substrates. Here, we show a minimal structural scaffold, the structural catalytic core (SCC), which is conserved within each family of acid proteases, but varies between families, and thus can serve as a structural marker of four individual protease families. The SCC is a dimer of several structural blocks, such as the DD-link, D-loop, and G-loop, around two catalytic aspartates in each protease subunit or an individual chain. A dimer made of two (D-loop + DD-link) structural elements makes a DD-zone, and the D-loop + G-loop combination makes a psi-loop. These structural markers are useful for protein comparison, structure identification, protein family separation, and protein engineering.

Original language	English
Article number	3451
Number of pages	19
Journal	Molecules
Volume	29
Issue number	15
DOIs	https://doi.org/10.3390/molecules29153451
Publication status	Published - 23 Jul 2024
MoE publication type	A2 Review article in a scientific journal

Funding

We thank the Biocenter Finland Bioinformatics Network (Jukka Lehtonen) and CSC IT Center for Science for computational support for the project. The Structural Bioinformatics Laboratory is part of the Solutions for Health strategic area of \u00C5bo Akademi University and within the InFLAMES Flagship program on inflammation and infection, \u00C5bo Akademi University and the University of Turku, funded by the Academy of Finland.

Keywords

Ddi1; Lpg0085
acid protease
active site
catalytic aspartate
pepsin; retropepsin

Access to Document

10.3390/molecules29153451

molecules-29-03451-v2Final published version, 4.88 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe20241213102314

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title = "Structural Catalytic Core of the Members of the Superfamily of Acid Proteases",

abstract = "The superfamily of acid proteases has two catalytic aspartates for proteolysis of their peptide substrates. Here, we show a minimal structural scaffold, the structural catalytic core (SCC), which is conserved within each family of acid proteases, but varies between families, and thus can serve as a structural marker of four individual protease families. The SCC is a dimer of several structural blocks, such as the DD-link, D-loop, and G-loop, around two catalytic aspartates in each protease subunit or an individual chain. A dimer made of two (D-loop + DD-link) structural elements makes a DD-zone, and the D-loop + G-loop combination makes a psi-loop. These structural markers are useful for protein comparison, structure identification, protein family separation, and protein engineering.",

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author = "Alexandre Denesyuk and Konstantin Denessiouk and Mark Johnson and Vladimir Uversky",

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T1 - Structural Catalytic Core of the Members of the Superfamily of Acid Proteases

AU - Denesyuk, Alexandre

AU - Denessiouk, Konstantin

AU - Johnson, Mark

AU - Uversky, Vladimir

PY - 2024/7/23

Y1 - 2024/7/23

N2 - The superfamily of acid proteases has two catalytic aspartates for proteolysis of their peptide substrates. Here, we show a minimal structural scaffold, the structural catalytic core (SCC), which is conserved within each family of acid proteases, but varies between families, and thus can serve as a structural marker of four individual protease families. The SCC is a dimer of several structural blocks, such as the DD-link, D-loop, and G-loop, around two catalytic aspartates in each protease subunit or an individual chain. A dimer made of two (D-loop + DD-link) structural elements makes a DD-zone, and the D-loop + G-loop combination makes a psi-loop. These structural markers are useful for protein comparison, structure identification, protein family separation, and protein engineering.

AB - The superfamily of acid proteases has two catalytic aspartates for proteolysis of their peptide substrates. Here, we show a minimal structural scaffold, the structural catalytic core (SCC), which is conserved within each family of acid proteases, but varies between families, and thus can serve as a structural marker of four individual protease families. The SCC is a dimer of several structural blocks, such as the DD-link, D-loop, and G-loop, around two catalytic aspartates in each protease subunit or an individual chain. A dimer made of two (D-loop + DD-link) structural elements makes a DD-zone, and the D-loop + G-loop combination makes a psi-loop. These structural markers are useful for protein comparison, structure identification, protein family separation, and protein engineering.

KW - Ddi1; Lpg0085

KW - acid protease

KW - active site

KW - catalytic aspartate

KW - pepsin; retropepsin

U2 - 10.3390/molecules29153451

DO - 10.3390/molecules29153451

M3 - Review Article or Literature Review

SN - 1420-3049

VL - 29

JO - Molecules

JF - Molecules

IS - 15

M1 - 3451

ER -

Structural Catalytic Core of the Members of the Superfamily of Acid Proteases

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