5ab3: Difference between revisions
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==S.enterica HisA mutant D7N, D10G, dup13-15, Q24L, G102A== | |||
<StructureSection load='5ab3' size='340' side='right'caption='[[5ab3]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ab3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Cubana_str._76814 Salmonella enterica subsp. enterica serovar Cubana str. 76814]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AB3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.803Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2ER:[(2R,3S,4R,5R)-5-[4-AMINOCARBONYL-5-[[(Z)-[(3R,4R)-3,4-DIHYDROXY-2-OXO-5-PHOSPHONOOXY-PENTYL]IMINOMETHYL]AMINO]IMIDAZOL-1-YL]-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+DIHYDROGEN+PHOSPHATE'>2ER</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ab3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ab3 OCA], [https://pdbe.org/5ab3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ab3 RCSB], [https://www.ebi.ac.uk/pdbsum/5ab3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ab3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HIS4_SALTY HIS4_SALTY] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
New genes can arise by duplication and divergence, but there is a fundamental gap in our understanding of the relationship between these genes, the evolving proteins they encode, and the fitness of the organism. Here we used crystallography, NMR dynamics, kinetics, and mass spectrometry to explain the molecular innovations that arose during a previous real-time evolution experiment. In that experiment, the (betaalpha)8 barrel enzyme HisA was under selection for two functions (HisA and TrpF), resulting in duplication and divergence of the hisA gene to encode TrpF specialists, HisA specialists, and bifunctional generalists. We found that selection affects enzyme structure and dynamics, and thus substrate preference, simultaneously and sequentially. Bifunctionality is associated with two distinct sets of loop conformations, each essential for one function. We observed two mechanisms for functional specialization: structural stabilization of each loop conformation and substrate-specific adaptation of the active site. Intracellular enzyme performance, calculated as the product of catalytic efficiency and relative expression level, was not linearly related to fitness. Instead, we observed thresholds for each activity above which further improvements in catalytic efficiency had little if any effect on growth rate. Overall, we have shown how beneficial substitutions selected during real-time evolution can lead to manifold changes in enzyme function and bacterial fitness. This work emphasizes the speed at which adaptive evolution can yield enzymes with sufficiently high activities such that they no longer limit the growth of their host organism, and confirms the (betaalpha)8 barrel as an inherently evolvable protein scaffold. | |||
Structural and functional innovations in the real-time evolution of new (betaalpha)8 barrel enzymes.,Newton MS, Guo X, Soderholm A, Nasvall J, Lundstrom P, Andersson DI, Selmer M, Patrick WM Proc Natl Acad Sci U S A. 2017 Apr 17. pii: 201618552. doi:, 10.1073/pnas.1618552114. PMID:28416687<ref>PMID:28416687</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ab3" style="background-color:#fffaf0;"></div> | ||
[[Category: Guo | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Salmonella enterica subsp. enterica serovar Cubana str. 76814]] | ||
[[Category: Andersson D]] | |||
[[Category: Guo X]] | |||
[[Category: Nasvall J]] | |||
[[Category: Newton M]] | |||
[[Category: Patrick W]] | |||
[[Category: Selmer M]] | |||
[[Category: Soderholm A]] | |||
Latest revision as of 14:06, 10 January 2024
S.enterica HisA mutant D7N, D10G, dup13-15, Q24L, G102AS.enterica HisA mutant D7N, D10G, dup13-15, Q24L, G102A
Structural highlights
FunctionPublication Abstract from PubMedNew genes can arise by duplication and divergence, but there is a fundamental gap in our understanding of the relationship between these genes, the evolving proteins they encode, and the fitness of the organism. Here we used crystallography, NMR dynamics, kinetics, and mass spectrometry to explain the molecular innovations that arose during a previous real-time evolution experiment. In that experiment, the (betaalpha)8 barrel enzyme HisA was under selection for two functions (HisA and TrpF), resulting in duplication and divergence of the hisA gene to encode TrpF specialists, HisA specialists, and bifunctional generalists. We found that selection affects enzyme structure and dynamics, and thus substrate preference, simultaneously and sequentially. Bifunctionality is associated with two distinct sets of loop conformations, each essential for one function. We observed two mechanisms for functional specialization: structural stabilization of each loop conformation and substrate-specific adaptation of the active site. Intracellular enzyme performance, calculated as the product of catalytic efficiency and relative expression level, was not linearly related to fitness. Instead, we observed thresholds for each activity above which further improvements in catalytic efficiency had little if any effect on growth rate. Overall, we have shown how beneficial substitutions selected during real-time evolution can lead to manifold changes in enzyme function and bacterial fitness. This work emphasizes the speed at which adaptive evolution can yield enzymes with sufficiently high activities such that they no longer limit the growth of their host organism, and confirms the (betaalpha)8 barrel as an inherently evolvable protein scaffold. Structural and functional innovations in the real-time evolution of new (betaalpha)8 barrel enzymes.,Newton MS, Guo X, Soderholm A, Nasvall J, Lundstrom P, Andersson DI, Selmer M, Patrick WM Proc Natl Acad Sci U S A. 2017 Apr 17. pii: 201618552. doi:, 10.1073/pnas.1618552114. PMID:28416687[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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