6rjb: Difference between revisions
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The | ==Human transketolase variant T382E== | ||
<StructureSection load='6rjb' size='340' side='right'caption='[[6rjb]], [[Resolution|resolution]] 1.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rjb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RJB FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TKT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transketolase Transketolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.2.1.1 2.2.1.1] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rjb OCA], [http://pdbe.org/6rjb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rjb RCSB], [http://www.ebi.ac.uk/pdbsum/6rjb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rjb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/TKT_HUMAN TKT_HUMAN]] Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The underlying molecular mechanisms of cooperativity and allosteric regulation are well understood for many proteins, with haemoglobin and aspartate transcarbamoylase serving as prototypical examples(1,2). The binding of effectors typically causes a structural transition of the protein that is propagated through signalling pathways to remote sites and involves marked changes on the tertiary and sometimes even the quaternary level(1-5). However, the origin of these signals and the molecular mechanism of long-range signalling at an atomic level remain unclear(5-8). The different spatial scales and timescales in signalling pathways render experimental observation challenging; in particular, the positions and movement of mobile protons cannot be visualized by current methods of structural analysis. Here we report the experimental observation of fluctuating low-barrier hydrogen bonds as switching elements in cooperativity pathways of multimeric enzymes. We have observed these low-barrier hydrogen bonds in ultra-high-resolution X-ray crystallographic structures of two multimeric enzymes, and have validated their assignment using computational calculations. Catalytic events at the active sites switch between low-barrier hydrogen bonds and ordinary hydrogen bonds in a circuit that consists of acidic side chains and water molecules, transmitting a signal through the collective repositioning of protons by behaving as an atomistic Newton's cradle. The resulting communication synchronizes catalysis in the oligomer. Our studies provide several lines of evidence and a working model for not only the existence of low-barrier hydrogen bonds in proteins, but also a connection to enzyme cooperativity. This finding suggests new principles of drug and enzyme design, in which sequences of residues can be purposefully included to enable long-range communication and thus the regulation of engineered biomolecules. | |||
Low-barrier hydrogen bonds in enzyme cooperativity.,Dai S, Funk LM, von Pappenheim FR, Sautner V, Paulikat M, Schroder B, Uranga J, Mata RA, Tittmann K Nature. 2019 Sep;573(7775):609-613. doi: 10.1038/s41586-019-1581-9. Epub 2019 Sep, 18. PMID:31534226<ref>PMID:31534226</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6rjb" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Transketolase]] | |||
[[Category: Pappenheim, F Rabe von]] | |||
[[Category: Tittmann, K]] | [[Category: Tittmann, K]] | ||
[[Category: | [[Category: Enzyme catalysis]] | ||
[[Category: Pentose phosphate pathway]] | |||
[[Category: Thiamin diphosphate]] | |||
[[Category: Transferase]] | |||
Revision as of 09:23, 10 October 2019
Human transketolase variant T382EHuman transketolase variant T382E
Structural highlights
Function[TKT_HUMAN] Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. Publication Abstract from PubMedThe underlying molecular mechanisms of cooperativity and allosteric regulation are well understood for many proteins, with haemoglobin and aspartate transcarbamoylase serving as prototypical examples(1,2). The binding of effectors typically causes a structural transition of the protein that is propagated through signalling pathways to remote sites and involves marked changes on the tertiary and sometimes even the quaternary level(1-5). However, the origin of these signals and the molecular mechanism of long-range signalling at an atomic level remain unclear(5-8). The different spatial scales and timescales in signalling pathways render experimental observation challenging; in particular, the positions and movement of mobile protons cannot be visualized by current methods of structural analysis. Here we report the experimental observation of fluctuating low-barrier hydrogen bonds as switching elements in cooperativity pathways of multimeric enzymes. We have observed these low-barrier hydrogen bonds in ultra-high-resolution X-ray crystallographic structures of two multimeric enzymes, and have validated their assignment using computational calculations. Catalytic events at the active sites switch between low-barrier hydrogen bonds and ordinary hydrogen bonds in a circuit that consists of acidic side chains and water molecules, transmitting a signal through the collective repositioning of protons by behaving as an atomistic Newton's cradle. The resulting communication synchronizes catalysis in the oligomer. Our studies provide several lines of evidence and a working model for not only the existence of low-barrier hydrogen bonds in proteins, but also a connection to enzyme cooperativity. This finding suggests new principles of drug and enzyme design, in which sequences of residues can be purposefully included to enable long-range communication and thus the regulation of engineered biomolecules. Low-barrier hydrogen bonds in enzyme cooperativity.,Dai S, Funk LM, von Pappenheim FR, Sautner V, Paulikat M, Schroder B, Uranga J, Mata RA, Tittmann K Nature. 2019 Sep;573(7775):609-613. doi: 10.1038/s41586-019-1581-9. Epub 2019 Sep, 18. PMID:31534226[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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