1r0m: Difference between revisions

Latest revision as of 13:29, 13 March 2024

Structure of Deinococcus radiodurans N-acylamino acid racemase at 1.3 : insights into a flexible binding pocket and evolution of enzymatic activity

Structural highlights

1r0m is a 4 chain structure with sequence from Deinococcus radiodurans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NSAR_DEIRA Acts as a N-succinylamino acid racemase (NSAR) that catalyzes the racemization of N-succinyl-L-phenylglycine and N-succinyl-D/L-phenylalanine (PubMed:24872444, PubMed:25875730). Can catalyze the racemization of a broad range of N-acylamino acids, including N-acetyl-D/L-methionine, N-acetyl-D/L-phenylalanine, N-acetyl-L-glutamine, N-acetyl-L-tryptophan, N-acetyl-L-leucine, N-formyl-D-methionine, N-formyl-D-norleucine, N-carbamoyl-D-methionine and N-carbamoyl-D-norleucine (PubMed:15313614, PubMed:16650857, PubMed:25875730). Also converts 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to 2-succinylbenzoate (OSB) (PubMed:24872444). Catalyzes both N-succinylamino acid racemization and OSB synthesis at equivalent rates (PubMed:24872444). However, NSAR activity is probably the protein's biological function, because menaquinone biosynthesis genes are missing in this species (Probable).^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Wang WC, Chiu WC, Hsu SK, Wu CL, Chen CY, Liu JS, Hsu WH. Structural basis for catalytic racemization and substrate specificity of an N-acylamino acid racemase homologue from Deinococcus radiodurans. J Mol Biol. 2004 Sep 3;342(1):155-69. PMID:15313614 doi:https://dx.doi.org/10.1016/j.jmb.2004.07.023
↑ Chiu WC, You JY, Liu JS, Hsu SK, Hsu WH, Shih CH, Hwang JK, Wang WC. Structure-stability-activity relationship in covalently cross-linked N-carbamoyl D-amino acid amidohydrolase and N-acylamino acid racemase. J Mol Biol. 2006 Jun 9;359(3):741-53. Epub 2006 Apr 18. PMID:16650857 doi:https://dx.doi.org/10.1016/j.jmb.2006.03.063
↑ Odokonyero D, Sakai A, Patskovsky Y, Malashkevich VN, Fedorov AA, Bonanno JB, Fedorov EV, Toro R, Agarwal R, Wang C, Ozerova ND, Yew WS, Sauder JM, Swaminathan S, Burley SK, Almo SC, Glasner ME. Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family. Proc Natl Acad Sci U S A. 2014 May 28. pii: 201318703. PMID:24872444 doi:https://dx.doi.org/10.1073/pnas.1318703111
↑ Soriano-Maldonado P, Andújar-Sánchez M, Clemente-Jiménez JM, Rodríguez-Vico F, Las Heras-Vázquez FJ, Martínez-Rodríguez S. Biochemical and Mutational Characterization of N-Succinyl-Amino Acid Racemase from Geobacillus stearothermophilus CECT49. Mol Biotechnol. 2015 May;57(5):454-65. PMID:25875730 doi:10.1007/s12033-015-9839-4
↑ Glasner ME, Fayazmanesh N, Chiang RA, Sakai A, Jacobson MP, Gerlt JA, Babbitt PC. Evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase family of the enolase superfamily. J Mol Biol. 2006 Jun 30;360(1):228-50. PMID:16740275 doi:10.1016/j.jmb.2006.04.055

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Wang WC, Chiu WC, Hsu SK, Wu CL, Chen CY, Liu JS, Hsu WH. Structural basis for catalytic racemization and substrate specificity of an N-acylamino acid racemase homologue from Deinococcus radiodurans. J Mol Biol. 2004 Sep 3;342(1):155-69. PMID:15313614 doi:https://dx.doi.org/10.1016/j.jmb.2004.07.023

[2] Chiu WC, You JY, Liu JS, Hsu SK, Hsu WH, Shih CH, Hwang JK, Wang WC. Structure-stability-activity relationship in covalently cross-linked N-carbamoyl D-amino acid amidohydrolase and N-acylamino acid racemase. J Mol Biol. 2006 Jun 9;359(3):741-53. Epub 2006 Apr 18. PMID:16650857 doi:https://dx.doi.org/10.1016/j.jmb.2006.03.063

[3] Odokonyero D, Sakai A, Patskovsky Y, Malashkevich VN, Fedorov AA, Bonanno JB, Fedorov EV, Toro R, Agarwal R, Wang C, Ozerova ND, Yew WS, Sauder JM, Swaminathan S, Burley SK, Almo SC, Glasner ME. Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family. Proc Natl Acad Sci U S A. 2014 May 28. pii: 201318703. PMID:24872444 doi:https://dx.doi.org/10.1073/pnas.1318703111

[4] Soriano-Maldonado P, Andújar-Sánchez M, Clemente-Jiménez JM, Rodríguez-Vico F, Las Heras-Vázquez FJ, Martínez-Rodríguez S. Biochemical and Mutational Characterization of N-Succinyl-Amino Acid Racemase from Geobacillus stearothermophilus CECT49. Mol Biotechnol. 2015 May;57(5):454-65. PMID:25875730 doi:10.1007/s12033-015-9839-4

[5] Glasner ME, Fayazmanesh N, Chiang RA, Sakai A, Jacobson MP, Gerlt JA, Babbitt PC. Evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase family of the enolase superfamily. J Mol Biol. 2006 Jun 30;360(1):228-50. PMID:16740275 doi:10.1016/j.jmb.2006.04.055

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[2]

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[5]

@@ Line 1: / Line 1: @@
-[[Image:1r0m.gif|left|200px]]<br /><applet load="1r0m" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1r0m, resolution 1.3&Aring;" />
-'''Structure of Deinococcus radiodurans N-acylamino acid racemase at 1.3 : insights into a flexible binding pocket and evolution of enzymatic activity'''<br />
-==Overview==
+==Structure of Deinococcus radiodurans N-acylamino acid racemase at 1.3 : insights into a flexible binding pocket and evolution of enzymatic activity==
-N-acylamino acid racemase (NAAAR) catalyzes the racemization of, N-acylamino acids and can be used in concert with an aminoacylase to, produce enantiopure alpha-amino acids, a process that has potential, industrial applications. Here we have cloned and characterized an NAAAR, homologue from a radiation-resistant ancient bacterium, Deinococcus, radiodurans. The expressed NAAAR racemized various substrates at an, optimal temperature of 60 degrees C and had Km values of 24.8 mM and 12.3, mM for N-acetyl-D-methionine and N-acetyl-L-methionine, respectively. The, crystal structure of NAAAR was solved to 1.3 A resolution using, multiwavelength anomalous dispersion (MAD) methods. The structure consists, of a homooctamer in which each subunit has an architecture characteristic, of enolases with a capping domain and a (beta/alpha)7 beta barrel domain., The NAAAR.Mg2+ and NAAAR.N-acetyl-L-glutamine.Mg2+ structures were also, determined, allowing us to define the Lys170-Asp195-Glu220-Asp245-Lys269, framework for catalyzing 1,1-proton exchange of N-acylamino acids. Four, subsites enclosing the substrate are identified: catalytic site, metal-binding site, side-chain-binding region, and a flexible lid region., The high conservation of catalytic and metal-binding sites in different, enolases reflects the essentiality of a common catalytic platform, allowing these enzymes to robustly abstract alpha-protons of various, carboxylate substrates efficiently. The other subsites involved in, substrate recognition are less conserved, suggesting that divergent, evolution has led to functionally distinct enzymes.
+<StructureSection load='1r0m' size='340' side='right'caption='[[1r0m]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[1r0m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R0M FirstGlance]. <br>
-R0M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R0M OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3&#8491;</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=1r0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r0m OCA], [https://pdbe.org/1r0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r0m RCSB], [https://www.ebi.ac.uk/pdbsum/1r0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r0m ProSAT]</span></td></tr>
-==Reference==
+</table>
-Structural basis for catalytic racemization and substrate specificity of an N-acylamino acid racemase homologue from Deinococcus radiodurans., Wang WC, Chiu WC, Hsu SK, Wu CL, Chen CY, Liu JS, Hsu WH, J Mol Biol. 2004 Sep 3;342(1):155-69. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15313614 15313614]
+== Function ==
+[https://www.uniprot.org/uniprot/NSAR_DEIRA NSAR_DEIRA] Acts as a N-succinylamino acid racemase (NSAR) that catalyzes the racemization of N-succinyl-L-phenylglycine and N-succinyl-D/L-phenylalanine (PubMed:24872444, PubMed:25875730). Can catalyze the racemization of a broad range of N-acylamino acids, including N-acetyl-D/L-methionine, N-acetyl-D/L-phenylalanine, N-acetyl-L-glutamine, N-acetyl-L-tryptophan, N-acetyl-L-leucine, N-formyl-D-methionine, N-formyl-D-norleucine, N-carbamoyl-D-methionine and N-carbamoyl-D-norleucine (PubMed:15313614, PubMed:16650857, PubMed:25875730). Also converts 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) to 2-succinylbenzoate (OSB) (PubMed:24872444). Catalyzes both N-succinylamino acid racemization and OSB synthesis at equivalent rates (PubMed:24872444). However, NSAR activity is probably the protein's biological function, because menaquinone biosynthesis genes are missing in this species (Probable).<ref>PMID:15313614</ref> <ref>PMID:16650857</ref> <ref>PMID:24872444</ref> <ref>PMID:25875730</ref> <ref>PMID:16740275</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r0/1r0m_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1r0m ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Deinococcus radiodurans]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Chen, C.Y.]]
+[[Category: Chen C-Y]]
-[[Category: Chiu, W.C.]]
+[[Category: Chiu W-C]]
-[[Category: Hsu, S.K.]]
+[[Category: Hsu S-K]]
-[[Category: Hsu, W.H.]]
+[[Category: Hsu W-H]]
-[[Category: Liu, J.S.]]
+[[Category: Liu J-S]]
-[[Category: Wang, W.C.]]
+[[Category: Wang W-C]]
-[[Category: Wu, C.L.]]
+[[Category: Wu C-L]]
-[[Category: racemase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 21:54:10 2007''

1r0m: Difference between revisions

Latest revision as of 13:29, 13 March 2024

Structure of Deinococcus radiodurans N-acylamino acid racemase at 1.3 : insights into a flexible binding pocket and evolution of enzymatic activity

Structural highlights

Function

Evolutionary Conservation

References

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