7agz

From Proteopedia

(Difference between revisions)

Revision as of 03:02, 21 April 2022

BsrV no-histagged

Structural highlights

7agz is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	Amino-acid racemase, with EC number 5.1.1.10
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BSR_VIBCH] Amino-acid racemase able to utilize a broad range of substrates. Reversibly racemizes ten of the 19 natural chiral amino acids known, including both non-beta-branched aliphatic amino acids (Ala, Leu, Met, Ser, Cys, Gln and Asn) and positively charged amino acids (His, Lys and Arg). Among these substrates, is the most efficient with lysine and arginine. Is also able to catalyze the racemization of several amino acids that are not typically incorporated into proteins such as ornithine and norleucine. Is not active on negatively charged (Glu and Asp) or aromatic (Tyr, Trp and Phe) amino acids and displays minimal activity towards beta-branched aliphatic (Ile, Val and Thr) substrates (PubMed:24419381). Enables bacteria to produce and release extracellular non-canonical D-amino acids (NCDAAs) that regulate diverse cellular processes which may function as part of a cooperative strategy in vibrio communities to protect non-producing members from competing bacteria (PubMed:29446806, PubMed:29028003). D-amino acid production by BsrV provides a cue for V.cholerae to decrease peptidoglycan synthesis and to alter its cell wall via incorporation of NCDAAs into the muropeptides, in adaption to stationary phase conditions (PubMed:19762646, PubMed:29028003).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Broad-spectrum amino acid racemases (Bsrs) enable bacteria to generate non-canonical D-amino acids (NCDAAs), whose roles and impact on microbial physiology, including modulation of cell wall structure and dissolution of biofilms, are just beginning to be appreciated. Here we used a diverse array of structural, biochemical and molecular simulation studies to define and characterize how BsrV is post-translationally regulated. We discovered that contrary to Vibrio cholerae alanine racemase AlrV highly compacted active site, BsrV's is broader and can be occupied by cell wall stem peptides. We found that peptidoglycan peptides modified with NCDAAs are better stabilized by BsrV's catalytic cavity and show better inhibitory capacity than canonical muropeptides. Notably, BsrV binding and inhibition can be recapitulated by undigested peptidoglycan sacculi as it exists in the cell. Docking simulations of BsrV binding the peptidoglycan polymer generate a model where the peptide stems are perfectly accommodated and stabilized within each of the dimers active sites. Taking these biochemical and structural data together, we propose that inhibition of BsrV by peptidoglycan peptides underlies a negative regulatory mechanism to avoid excessive NCDAA production. Our results collectively open the door to use "a la carte" synthetic peptides as a tool to modulate DAAs production of Bsr enzymes.

Binding of non-canonical peptidoglycan controls Vibrio cholerae broad spectrum racemase activity.,Espaillat A, Carrasco-Lopez C, Bernardo-Garcia N, Rojas-Altuve A, Klett J, Morreale A, Hermoso JA, Cava F Comput Struct Biotechnol J. 2021 Jan 26;19:1119-1126. doi:, 10.1016/j.csbj.2021.01.031. eCollection 2021. PMID:33680355^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lam H, Oh DC, Cava F, Takacs CN, Clardy J, de Pedro MA, Waldor MK. D-amino acids govern stationary phase cell wall remodeling in bacteria. Science. 2009 Sep 18;325(5947):1552-5. doi: 10.1126/science.1178123. PMID:19762646 doi:http://dx.doi.org/10.1126/science.1178123
↑ Espaillat A, Carrasco-Lopez C, Bernardo-Garcia N, Pietrosemoli N, Otero LH, Alvarez L, de Pedro MA, Pazos F, Davis BM, Waldor MK, Hermoso JA, Cava F. Structural basis for the broad specificity of a new family of amino-acid racemases. Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):79-90. doi:, 10.1107/S1399004713024838. Epub 2013 Dec 24. PMID:24419381 doi:http://dx.doi.org/10.1107/S1399004713024838
↑ Alvarez L, Aliashkevich A, de Pedro MA, Cava F. Bacterial secretion of D-arginine controls environmental microbial biodiversity. ISME J. 2018 Feb;12(2):438-450. doi: 10.1038/ismej.2017.176. Epub 2017 Oct 13. PMID:29028003 doi:http://dx.doi.org/10.1038/ismej.2017.176
↑ Cava F. Divergent functional roles of D-amino acids secreted by Vibrio cholerae. Int Microbiol. 2017 Sep;20(3):149-150. doi: 10.2436/20.1501.01.296. PMID:29446806 doi:http://dx.doi.org/10.2436/20.1501.01.296
↑ Espaillat A, Carrasco-Lopez C, Bernardo-Garcia N, Rojas-Altuve A, Klett J, Morreale A, Hermoso JA, Cava F. Binding of non-canonical peptidoglycan controls Vibrio cholerae broad spectrum racemase activity. Comput Struct Biotechnol J. 2021 Jan 26;19:1119-1126. doi:, 10.1016/j.csbj.2021.01.031. eCollection 2021. PMID:33680355 doi:http://dx.doi.org/10.1016/j.csbj.2021.01.031

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7agz"

@@ Line 1: / Line 1: @@
 ==BsrV no-histagged==
-<StructureSection load='7agz' size='340' side='right'caption='[[7agz]]' scene=''>
+<StructureSection load='7agz' size='340' side='right'caption='[[7agz]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7agz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AGZ FirstGlance]. <br>
-</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=7agz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7agz OCA], [https://pdbe.org/7agz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7agz RCSB], [https://www.ebi.ac.uk/pdbsum/7agz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7agz ProSAT]</span></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Amino-acid_racemase Amino-acid racemase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.10 5.1.1.10] </span></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=7agz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7agz OCA], [https://pdbe.org/7agz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7agz RCSB], [https://www.ebi.ac.uk/pdbsum/7agz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7agz ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[https://www.uniprot.org/uniprot/BSR_VIBCH BSR_VIBCH]] Amino-acid racemase able to utilize a broad range of substrates. Reversibly racemizes ten of the 19 natural chiral amino acids known, including both non-beta-branched aliphatic amino acids (Ala, Leu, Met, Ser, Cys, Gln and Asn) and positively charged amino acids (His, Lys and Arg). Among these substrates, is the most efficient with lysine and arginine. Is also able to catalyze the racemization of several amino acids that are not typically incorporated into proteins such as ornithine and norleucine. Is not active on negatively charged (Glu and Asp) or aromatic (Tyr, Trp and Phe) amino acids and displays minimal activity towards beta-branched aliphatic (Ile, Val and Thr) substrates (PubMed:24419381). Enables bacteria to produce and release extracellular non-canonical D-amino acids (NCDAAs) that regulate diverse cellular processes which may function as part of a cooperative strategy in vibrio communities to protect non-producing members from competing bacteria (PubMed:29446806, PubMed:29028003). D-amino acid production by BsrV provides a cue for V.cholerae to decrease peptidoglycan synthesis and to alter its cell wall via incorporation of NCDAAs into the muropeptides, in adaption to stationary phase conditions (PubMed:19762646, PubMed:29028003).<ref>PMID:19762646</ref> <ref>PMID:24419381</ref> <ref>PMID:29028003</ref> <ref>PMID:29446806</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Broad-spectrum amino acid racemases (Bsrs) enable bacteria to generate non-canonical D-amino acids (NCDAAs), whose roles and impact on microbial physiology, including modulation of cell wall structure and dissolution of biofilms, are just beginning to be appreciated. Here we used a diverse array of structural, biochemical and molecular simulation studies to define and characterize how BsrV is post-translationally regulated. We discovered that contrary to Vibrio cholerae alanine racemase AlrV highly compacted active site, BsrV's is broader and can be occupied by cell wall stem peptides. We found that peptidoglycan peptides modified with NCDAAs are better stabilized by BsrV's catalytic cavity and show better inhibitory capacity than canonical muropeptides. Notably, BsrV binding and inhibition can be recapitulated by undigested peptidoglycan sacculi as it exists in the cell. Docking simulations of BsrV binding the peptidoglycan polymer generate a model where the peptide stems are perfectly accommodated and stabilized within each of the dimers active sites. Taking these biochemical and structural data together, we propose that inhibition of BsrV by peptidoglycan peptides underlies a negative regulatory mechanism to avoid excessive NCDAA production. Our results collectively open the door to use "a la carte" synthetic peptides as a tool to modulate DAAs production of Bsr enzymes.
+Binding of non-canonical peptidoglycan controls Vibrio cholerae broad spectrum racemase activity.,Espaillat A, Carrasco-Lopez C, Bernardo-Garcia N, Rojas-Altuve A, Klett J, Morreale A, Hermoso JA, Cava F Comput Struct Biotechnol J. 2021 Jan 26;19:1119-1126. doi:, 10.1016/j.csbj.2021.01.031. eCollection 2021. PMID:33680355<ref>PMID:33680355</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7agz" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Amino-acid racemase]]
 [[Category: Large Structures]]
-[[Category: Carrasco-Lopez C]]
+[[Category: Carrasco-Lopez, C]]
-[[Category: Cava F]]
+[[Category: Cava, F]]
-[[Category: Espaillat A]]
+[[Category: Espaillat, A]]
-[[Category: Hermoso JA]]
+[[Category: Hermoso, J A]]
-[[Category: Rojas-Altuve A]]
+[[Category: Rojas-Altuve, A]]
+[[Category: Broad spectrum]]
+[[Category: Peptide binding protein]]
+[[Category: Peptidoglycan binding protein]]
+[[Category: Racemase]]

7agz

From Proteopedia

Revision as of 03:02, 21 April 2022

BsrV no-histagged

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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