Enzyme catalysis prior to aromatic residues: Reverse engineering of a dephospho‐CoA kinase

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00541647" target="_blank" >RIV/61388963:_____/21:00541647 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/21:10439001 RIV/00216224:14740/21:00124510

Result on the web

<a href="https://doi.org/10.1002/pro.4068" target="_blank" >https://doi.org/10.1002/pro.4068</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/pro.4068" target="_blank" >10.1002/pro.4068</a>

Result language

angličtina

Original language name

Enzyme catalysis prior to aromatic residues: Reverse engineering of a dephospho‐CoA kinase

Original language description

The wide variety of protein structures and functions results from the diverse properties of the 20 canonical amino acids. The generally accepted hypothesis is that early protein evolution was associated with enrichment of a primordial alphabet, thereby enabling increased protein catalytic efficiencies and functional diversification. Aromatic amino acids were likely among the last additions to genetic code. The main objective of this study was to test whether enzyme catalysis can occur without the aromatic residues (aromatics) by studying the structure and function of dephospho‐CoA kinase (DPCK) following aromatic residue depletion. We designed two variants of a putative DPCK from Aquifex aeolicus by substituting (a) Tyr, Phe and Trp or (b) all aromatics (including His). Their structural characterization indicates that substituting the aromatics does not markedly alter their secondary structures but does significantly loosen their side chain packing and increase their sizes. Both variants still possess ATPase activity, although with 150–300 times lower efficiency in comparison with the wild‐type phosphotransferase activity. The transfer of the phosphate group to the dephospho‐CoA substrate becomes heavily uncoupled and only the His‐containing variant is still able to perform the phosphotransferase reaction. These data support the hypothesis that proteins in the early stages of life could support catalytic activities, albeit with low efficiencies. An observed significant contraction upon ligand binding is likely important for appropriate organization of the active site. Formation of firm hydrophobic cores, which enable the assembly of stably structured active sites, is suggested to provide a selective advantage for adding the aromatic residues.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Protein Science

ISSN

0961-8368

e-ISSN

1469-896X

Volume of the periodical

30

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

1022-1034

UT code for WoS article

000632928300001

EID of the result in the Scopus database

2-s2.0-85103210737