The interdimeric interface controls function and stability of Ureaplasma urealiticum methionine S-adenosyltransferase

Kleiner, Daniel; Shmulevich, Fannia; Zarivach, Raz; Shahar, Amit; Sharon, Michal; Ben‐Nissan, Gili; Bershtein, Shimon

doi:10.1016/j.jmb.2019.09.003

Cited by 16 publications

(19 citation statements)

References 67 publications

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“…The unfolding data also show that the dimer of PCP6 is more stable than that of PCP7 or of PCP-CA, where the mid-point of dimer dissociation is approximately 5 M urea for PCP6 versus 2 M urea for PCP7 and PCP-CA, likely due to the higher population of the I2 intermediate in PCP6 compared to PCP7 and PCP-CA. Notably, Matthews and others (42,43) have reported that amino acid substitutions that change in the number of salt bridges in the native structure of a protein are a key parameter in modulating the free energy landscape of a protein fold. We compared the number of salt bridges among extant caspases using a protein tool developed by Ferruz et al (44).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, Matthews et al. ( 42 , 43 ) have reported that amino acid substitutions that change in the number of salt bridges in the native structure of a protein are a key parameter in modulating the free energy landscape of a protein fold. We compared the number of salt bridges among extant caspases using a protein tool developed by Ferruz et al.…”

Section: Discussionmentioning

confidence: 99%

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Evolution of the folding landscape of effector caspases

Shrestha¹,

Clark²

2021

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evolution of the folding landscape of effector caspases

Shrestha¹,

Clark²

2021

Journal of Biological Chemistry

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“…In case of MAT enzymes, the constituent monomers pair up in an inverted configuration by exposing the α-helices towards the surface and the β-strands interact to form a hydrophobic isologous large interface that harbor the catalytic residues – thereby making this homo-dimer the obligate functional unit 27 . Herein, we notice that divergence is not just limited to catalytic residues, or the residues located close to the substrate, but most of the inter-dimer interface (large-interface) residues are also quite diverged across the three domains of life, for instance - in case of bacteria (eMAT, PDB: 1RG9, 28 ) and eukarya (hMAT1A, PDB:6SW5, 29 ) - 38 out of 51 aligned residues are identical.…”

Section: Resultsmentioning

confidence: 99%

Consequences of the divergence of Methionine AdenosylTransferase

Chouhan

Gade

Martinez

et al. 2020

Preprint

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Methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine from L-methionine and ATP, is an ancient, highly conserved enzyme present in all three domains of life. Although the MAT enzymes of each domain are believed to share a common ancestor, the sequences of archaeal MATs show a high degree of divergence from the sequences of bacterial and eukaryotic MATs. However, the structural and functional consequences of this sequence divergence are not well understood. Here, we use structural bioinformatics analysis and ancestral sequence reconstruction to analyze the evolution of archaeal MATs. We show that the dimer interface containing the active site, which would be expected to be well conserved across all three domains, diverged considerably between the bacterial/eukaryotic MATs and archaeal MATs. Furthermore, the characterization of reconstructed ancestral archaeal MATs showed that they probably had low substrate specificity which expanded during their evolutionary trajectory hinting towards the observation that all the modern day MAT enzymes from the three-kingdom probably originated from a common specific ancestor and then archaea MATs diverged in sequence, structure and substrate specificity. Altogether, our results show that the archaea MAT is an ideal system for studying an enzyme family which evolved to display high degrees of divergence at the sequence/structural levels and yet are capable of performing the same catalytic reactions as their orthologous counterparts.

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“…The unfolding data also show that the dimer of PCP6 is more stable than that of PCP7 or of PCP-CA, where the mid-point of dimer dissociation is approximately 5 M urea for PCP6 versus 2 M urea for PCP7 and PCP-CA, likely due to the higher population of the I2 intermediate in PCP6 compared to PCP7 and PCP-CA. Notably, Matthews and others (40,41) have reported that amino acid substitutions that change in the number of salt bridges in the native structure of a protein are a key parameter in modulating the free energy landscape of a protein fold. We compared the number of salt bridges among extant caspases using a protein tool developed by Ferruz et al (42).…”

Section: Discussionmentioning

confidence: 99%

Evolution of the folding landscape of effector caspases

Shrestha

Clark

2021

Preprint

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Caspases are a family of cysteinyl proteases that control programmed cell death and maintain homeostasis in multicellular organisms. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens (procaspases) that must be activated to gain full activity; the protein structures are conserved through hundreds of millions of years of evolution; and some allosteric features arose with the early ancestor while others are more recent evolutionary events. The apoptotic caspases evolved from a common ancestor into two distinct subfamilies: monomers (initiator caspases) or dimers (effector caspases). Differences in activation mechanisms of the two subfamilies, and their oligomeric forms, play a central role in the regulation of apoptosis. Here, we examine changes in the folding landscape by characterizing human effector caspases and their common ancestor. The results show that the effector caspases unfold by a minimum three-state equilibrium model at pH 7.5, where the native dimer is in equilibrium with a partially folded monomeric (procaspase-7, common ancestor) or dimeric (procaspase-6) intermediate. In comparison, the unfolding pathway of procaspase-3 contains both oligomeric forms of the intermediate. Overall, the data show that the folding landscape was first established with the common ancestor and was then retained for >650 million years. Partially folded monomeric or dimeric intermediates in the ancestral ensemble provide mechanisms for evolutionary changes that affect stability of extant caspases. The conserved folding landscape allows for the fine-tuning of enzyme stability in a species-dependent manner while retaining the overall caspase-hemoglobinase fold.

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The interdimeric interface controls function and stability of Ureaplasma urealiticum methionine S-adenosyltransferase

Cited by 16 publications

References 67 publications

Evolution of the folding landscape of effector caspases

Evolution of the folding landscape of effector caspases

Consequences of the divergence of Methionine AdenosylTransferase

Evolution of the folding landscape of effector caspases

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