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^*

^*Korresponderande författare för detta arbete

Forskningsoutput: Tidskriftsbidrag › Översiktsartikel › Peer review

3 Citeringar (Scopus)

137 Nedladdningar (Pure)

Sammanfattning

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.

Originalspråk	Engelska
Artikelnummer	3451
Antal sidor	19
Tidskrift	Molecules
Volym	29
Nummer	15
DOI	https://doi.org/10.3390/molecules29153451
Status	Publicerad - 23 juli 2024
MoE-publikationstyp	A2 Översiktsartikel artikel i en vetenskaplig tidskrift

Finansiering

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.

Åtkomst av dokument

10.3390/molecules29153451

molecules-29-03451-v2Slutlig publicerad version, 4,88 MBLicens: 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.",

keywords = "Ddi1; Lpg0085, acid protease, active site, catalytic aspartate, pepsin; retropepsin",

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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