8af3
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Sterol carrier protein Artifical metalloenzyme incorporating Q111C mutation coupled to 2,2'-bipyridine== | |
| + | <StructureSection load='8af3' size='340' side='right'caption='[[8af3]], [[Resolution|resolution]] 1.52Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8af3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AF3 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]] 1.52Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=Q8X:(2~{R})-2-azanyl-3-[(6-pyridin-2-ylpyridin-3-yl)methylsulfanyl]propanal'>Q8X</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</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=8af3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8af3 OCA], [https://pdbe.org/8af3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8af3 RCSB], [https://www.ebi.ac.uk/pdbsum/8af3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8af3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN] Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:[https://omim.org/entry/261515 261515]. DBPD is a disorder of peroxisomal fatty acid beta-oxidation.<ref>PMID:9482850</ref> <ref>PMID:10400999</ref> <ref>PMID:11743515</ref> Defects in HSD17B4 are the cause of Perrault syndrome (PRLTS1) [MIM:[https://omim.org/entry/233400 233400]. A sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement.<ref>PMID:20673864</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN] Bifunctional enzyme acting on the peroxisomal beta-oxidation pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids.<ref>PMID:9089413</ref> <ref>PMID:8902629</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Artificial metalloenzymes (ArMs) have emerged as a promising avenue in the field of biocatalysis, offering new reactivity. However, their design remains challenging due to the limited understanding of their protein dynamics and how the introduced cofactors alter the protein scaffold structure. Here we present the structures and catalytic activity of novel copper ArMs capable of (R)- or (S)-stereoselective control, utilizing a steroid carrier protein (SCP) scaffold. To incorporate 2,2'-bipyridine (Bpy) into SCP, two distinct strategies were employed: either Bpy was introduced as an unnatural amino acid (2,2'-bipyridin-5-yl)alanine (BpyAla) using amber stop codon expression or via bioconjugation of bromomethyl-Bpy to cysteine residues. The resulting ArMs proved to be effective at catalysing an enantioselective Friedel-Crafts reaction with SCP_Q111BpyAla achieving the best selectivity with an enantioselectivity of 72% ee (S). Interestingly, despite using the same protein scaffold, different attachment strategies for Bpy at the same residue (Q111) led to a switch in the enantiopreference of the ArM. X-ray crystal structures of SCP_Q111CBpy and SCP_Q111BpyAla ArMs with bound Cu(ii) ions unveiled crucial differences in the orientation of the catalytic centre. Combining structural information, alanine scanning studies, and computational analysis shed light on the distinct active sites of the ArMs, clarifying that these active sites stabilise the nucleophilic substrate on different sides of the electrophile leading to the observed switch in enantioselectivity. This work underscores the importance of integrating structural studies with catalytic screening to unravel the intricacies of ArM behaviour and facilitate their development for targeted applications in biocatalysis. | ||
| - | + | Using BpyAla to generate copper artificial metalloenzymes: a catalytic and structural study.,Klemencic E, Brewster RC, Ali HS, Richardson JM, Jarvis AG Catal Sci Technol. 2024 Jan 29;14(6):1622-1632. doi: 10.1039/d3cy01648j. , eCollection 2024 Mar 18. PMID:38505507<ref>PMID:38505507</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8af3" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Jarvis AG]] | ||
| + | [[Category: Klemencic E]] | ||
| + | [[Category: Richardson JM]] | ||
Current revision
Sterol carrier protein Artifical metalloenzyme incorporating Q111C mutation coupled to 2,2'-bipyridine
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