The evolutionary history of the HUP domain

Gruić-Sovulj, Ita; Longo, Liam M.; Jabłońska, Jagoda; Tawfik, Dan S.

doi:10.1080/10409238.2021.1957764

Cited by 9 publications

(21 citation statements)

References 39 publications

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“…Substrate-handle binding might have been the ancestral function of the Rossmann and ferredoxin folds, as well as some superfamilies that adopted the TIM-barrel fold including the aldolase superfamily (Figure 1b). In other lineages, most notably in the P-loop NTPases 20 and HUP lineages, 29 phosphate is part of the chemistry. Other examples of substrate-binding-first families include the HAD 30 and ribonuclease H 31,32 lineages.…”

Section: Phosphate Binding Is a Primordial Protein Functionmentioning

confidence: 99%

Uniform binding and negative catalysis at the origin of enzymes

et al. 2022

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Enzymes are well known for their catalytic abilities, some even reaching “catalytic perfection” in the sense that the reaction they catalyze has reached the physical bound of the diffusion rate. However, our growing understanding of enzyme superfamilies has revealed that only some share a catalytic chemistry while others share a substrate‐handle binding motif, for example, for a particular phosphate group. This suggests that some families emerged through a “substrate‐handle‐binding‐first” mechanism (“binding‐first” for brevity) instead of “chemistry‐first” and we are, therefore, left to wonder what the role of non‐catalytic binders might have been during enzyme evolution. In the last of their eight seminal, back‐to‐back articles from 1976, John Albery and Jeremy Knowles addressed the question of enzyme evolution by arguing that the simplest mode of enzyme evolution is what they defined as “uniform binding” (parallel stabilization of all enzyme‐bound states to the same degree). Indeed, we show that a uniform‐binding proto‐catalyst can accelerate a reaction, but only when catalysis is already present, that is, when the transition state is already stabilized to some degree. Thus, we sought an alternative explanation for the cases where substrate‐handle‐binding preceded any involvement of a catalyst. We find that evolutionary starting points that exhibit negative catalysis can redirect the reaction's course to a preferred product without need for rate acceleration or product release; that is, if they do not stabilize, or even destabilize, the transition state corresponding to an undesired product. Such a mechanism might explain the emergence of “binding‐first” enzyme families like the aldolase superfamily.

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Section: Phosphate Binding Is a Primordial Protein Functionmentioning

confidence: 99%

Uniform binding and negative catalysis at the origin of enzymes

et al. 2022

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“…Shown are the major splits inferred in our previous work 28 and here, and the key ancestral nodes. The analysis described here focuses on HIGH nucleotidyl pyrophosphate transferases (HIGH-NTPs), which comprise two major Clades, 1 and 2, denoted by circles.…”

Section: Resultsmentioning

confidence: 87%

“…The origin of Class I AARS is well defined within the HUP’s phylogenetic tree, which indicates that PP-ATPases emerged first, and later gave rise to HIGH nucleotidyl pyrophosphate transferases (HIGH-NTPs, Fig. 1 ) 28 . HIGH-NTPs split into two subclades: Clade 1 comprises all Class I AARSs and Clade 2 includes the ATP/CTP-dependent ligases.…”

Section: Resultsmentioning

confidence: 99%

“…As expected, this ‘seed’ alignment captured the two known Class I signature motifs (HIGH, KMSKS), as well as a GxD motif on the loop connecting β4 and α4. The latter mediates binding of the ribose moiety of ATP and is a hallmark of the HIGH-NPTs (present in both Clade 1, AARRs, and Clade 2) 28 .…”

Section: Resultsmentioning

confidence: 99%

“…We opted for class I AARSs as the evolutionary and functional context in which Class I emerged is tractable. The synthetic domain of Class I AARSs belongs to the ancient HUP superfamily 27,28 , comprising predominantly ligases that use ATP to activate various substrates via a substrate-AMP intermediate. To provide a reliable structure-based sequence alignment we selected the most conserved catalytic core of the class I synthetic domain, which includes the amino acid and ATP binding sites.…”

Section: Introductionmentioning

confidence: 99%

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The evolutionary history of class I aminoacyl-tRNA synthetases indicates early statistical translation

Jabłońska

Chun-Chen

Longo

et al. 2022

Preprint

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How protein translation evolved from a simple beginning to its complex and accurate contemporary state is unknown. Aminoacyl-tRNA synthetases (AARSs) define the genetic code by activating amino acids and loading them onto cognate tRNAs. As such, their evolutionary history can shed light on early translation. Using structure-based alignments of the conserved core of Class I AARSs, we reconstructed their phylogenetic tree and ancestral states. Unexpectedly, AARSs charging amino acids that are assumed to have emerged later - such as TrpRS and TyrRS or LysRS and CysRS - appear as the earliest splits in the tree; conversely, those AARSs charging abiotic, early-emerging amino acids, e.g. ValRS, seem to have diverged most recently. Furthermore, the inferred Class I ancestor (excluding TrpRS and TyrRS) lacks the residues that mediate selectivity in contemporary AARSs, and appears to be a generalist that could charge a wide range of amino acids. This ancestor subsequently diverged to two clades: "charged" (which gave rise to ArgRS, GluRS, and GlnRS) and "hydrophobics", which includes CysRS and LysRS as its outgroups. The ancestors of both clades maintain a wide-accepting pocket that could readily diverge to the contemporary, specialized families. Overall, our findings suggest a "generalist-maintaining" model of class I AARS evolution, in which early statistical translation was kept active by a generalist AARS while the evolution of a specialized, accurate translation system took place.

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An evolutionary history of the CoA‐binding protein Nat/Ivy

2022

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Nat/Ivy is a diverse and ubiquitous CoA‐binding evolutionary lineage that catalyzes acyltransferase reactions, primarily converting thioesters into amides. At the heart of the Nat/Ivy fold is a phosphate‐binding loop that bears a striking resemblance to that of P‐loop NTPases—both are extended, glycine‐rich loops situated between a β‐strand and an α‐helix. Nat/Ivy, therefore, represents an intriguing intersection between thioester chemistry, a putative primitive energy currency, and an ancient mode of phospho‐ligand binding. Current evidence suggests that Nat/Ivy emerged independently of other cofactor‐utilizing enzymes, and that the observed structural similarity—particularly of the cofactor binding site—is the product of shared constraints instead of shared ancestry. The reliance of Nat/Ivy on a β‐α‐β motif for CoA‐binding highlights the extent to which this simple structural motif may have been a fundamental evolutionary “nucleus” around which modern cofactor‐binding domains condensed, as has been suggested for HUP domains, Rossmanns, and P‐loop NTPases. Finally, by dissecting the patterns of conserved interactions between Nat/Ivy families and CoA, the coevolution of the enzyme and the cofactor was analyzed. As with the Rossmann, it appears that the pyrophosphate moiety at the center of the cofactor predates the enzyme, suggesting that Nat/Ivy emerged sometime after the metabolite dephospho‐CoA.

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The evolutionary history of the HUP domain

Cited by 9 publications

References 39 publications

Uniform binding and negative catalysis at the origin of enzymes

Uniform binding and negative catalysis at the origin of enzymes

The evolutionary history of class I aminoacyl-tRNA synthetases indicates early statistical translation

An evolutionary history of the CoA‐binding protein Nat/Ivy

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