1l4h: Difference between revisions

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New page: left|200px<br /><applet load="1l4h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l4h, resolution 2.10Å" /> '''Crystal Structure of...
 
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[[Image:1l4h.gif|left|200px]]<br /><applet load="1l4h" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1l4h, resolution 2.10&Aring;" />
'''Crystal Structure of CobT complexed with indole and nicotinate mononucleotide'''<br />


==Overview==
==Crystal Structure of CobT complexed with indole and nicotinate mononucleotide==
The evolution of biosynthetic pathways is difficult to reconstruct in, hindsight; however, the structures of the enzymes that are involved may, provide insight into their development. One enzyme in the cobalamin, biosynthetic pathway that appears to have evolved from a protein with, different function is L-threonine-O-3-phosphate decarboxylase (CobD) from, Salmonella enterica, which is structurally similar to histidinol phosphate, aminotransferase [Cheong, C. G., Bauer, C. B., Brushaber, K. R., Escalante-Semerena, J. C., and Rayment, I. (2002) Biochemistry 41, 4798-4808]. This enzyme is responsible for synthesizing, (R)-1-amino-2-propanol phosphate which is the precursor for the linkage, between the nucleotide loop and the corrin ring in cobalamin. To, understand the relationship between this decarboxylase and the aspartate, aminotransferase family to which it belongs, the structures of CobD in its, apo state, the apo state complexed with the substrate, and its product, external aldimine complex have been determined at 1.46, 1.8, and 1.8 A, resolution, respectively. These structures show that the enzyme steers the, breakdown of the external aldimine toward decarboxylation instead of amino, transfer by positioning the carboxylate moiety of the substrate out of the, plane of the pyridoxal ring and by placing the alpha-hydrogen out of reach, of the catalytic base provided by the lysine that forms the internal, aldimine. It would appear that CobD evolved from a primordial, PLP-dependent aminotransferase, where the selection was based on, similarities between the stereochemical properties of the substrates, rather than preservation of the fate of the external aldimine. These, structures provide a sequence signature for distinguishing between, L-threonine-O-3-phosphate decarboxylase and histidinol phosphate, aminotransferases, many of which appear to have been misannotated.
<StructureSection load='1l4h' size='340' side='right'caption='[[1l4h]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1l4h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L4H 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IND:INDOLE'>IND</scene>, <scene name='pdbligand=NCN:NICOTINATE+MONONUCLEOTIDE'>NCN</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=1l4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l4h OCA], [https://pdbe.org/1l4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l4h RCSB], [https://www.ebi.ac.uk/pdbsum/1l4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l4h ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/COBT_SALTY COBT_SALTY] Catalyzes the synthesis of alpha-ribazole-5'-phosphate from nicotinate mononucleotide (NAMN) and 5,6-dimethylbenzimidazole (DMB).
== 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/l4/1l4h_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1l4h ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in the synthesis of alpha-ribazole-5'-phosphate, an intermediate for the lower ligand of cobalamin. In earlier studies it proved difficult to obtain the structure of CobT bound to NaMN because it is hydrolyzed in the crystal lattice in the absence of the second substrate DMB. In an effort to map the reaction pathway of this enzyme, NaMN was captured in the active site with the substrate analogs 4,5-dimethyl-1,2-phenylenediamine, 4-methylcatechol, indole, 3,4-dimethylaniline, 2,5-dimethylaniline, 3,4-dimethylphenol, and 2-amino-p-cresol. Structures of these complexes reveal that they exclude water molecules responsible for the hydrolysis from the active site. These structures, together with the early complexes with alpha-ribazole-5'-phosphate and DMB, provide a complete description of the reaction pathway. They demonstrate that the nicotinate moiety and phosphate do not appear to move significantly between reactants and products but that the aromatic base and ribose moiety each move approximately 1.2 A toward each other in the transformation. This study also reveals that, like many other nucleotide binding proteins, coordination of DMB is accompanied by a disorder-order transition in a surface loop. The structure of apo-CobT is also reported.


==About this Structure==
Capture of a labile substrate by expulsion of water molecules from the active site of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica.,Cheong CG, Escalante-Semerena JC, Rayment I J Biol Chem. 2002 Oct 25;277(43):41120-7. Epub 2002 Jul 5. PMID:12101181<ref>PMID:12101181</ref>
1L4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_enterica Salmonella enterica] with IND and NCN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nicotinate-nucleotide--dimethylbenzimidazole_phosphoribosyltransferase Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.21 2.4.2.21] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L4H OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural studies of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica: the apo, substrate, and product-aldimine complexes., Cheong CG, Escalante-Semerena JC, Rayment I, Biochemistry. 2002 Jul 23;41(29):9079-89. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12119022 12119022]
</div>
[[Category: Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase]]
<div class="pdbe-citations 1l4h" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Salmonella enterica]]
[[Category: Salmonella enterica]]
[[Category: Single protein]]
[[Category: Cheong C-G]]
[[Category: Cheong, C.G.]]
[[Category: Escalante-Semerena J]]
[[Category: Escalante-Semerena, J.]]
[[Category: Rayment I]]
[[Category: Rayment, I.]]
[[Category: IND]]
[[Category: NCN]]
[[Category: 5]]
[[Category: 6-dimethylbenzimidazole]]
[[Category: cobalamin synthetic enzyme]]
[[Category: cobt]]
[[Category: nicotinate mononucleotide]]
[[Category: phosphoribosyltransferase]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:15:05 2007''

Latest revision as of 09:56, 30 October 2024

Crystal Structure of CobT complexed with indole and nicotinate mononucleotideCrystal Structure of CobT complexed with indole and nicotinate mononucleotide

Structural highlights

1l4h is a 1 chain structure with sequence from Salmonella enterica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

COBT_SALTY Catalyzes the synthesis of alpha-ribazole-5'-phosphate from nicotinate mononucleotide (NAMN) and 5,6-dimethylbenzimidazole (DMB).

Evolutionary Conservation

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

Publication Abstract from PubMed

Nicotinate mononucleotide (NaMN):5,6-dimethylbenzimidazole (DMB) phosphoribosyltransferase (CobT) from Salmonella enterica plays a central role in the synthesis of alpha-ribazole-5'-phosphate, an intermediate for the lower ligand of cobalamin. In earlier studies it proved difficult to obtain the structure of CobT bound to NaMN because it is hydrolyzed in the crystal lattice in the absence of the second substrate DMB. In an effort to map the reaction pathway of this enzyme, NaMN was captured in the active site with the substrate analogs 4,5-dimethyl-1,2-phenylenediamine, 4-methylcatechol, indole, 3,4-dimethylaniline, 2,5-dimethylaniline, 3,4-dimethylphenol, and 2-amino-p-cresol. Structures of these complexes reveal that they exclude water molecules responsible for the hydrolysis from the active site. These structures, together with the early complexes with alpha-ribazole-5'-phosphate and DMB, provide a complete description of the reaction pathway. They demonstrate that the nicotinate moiety and phosphate do not appear to move significantly between reactants and products but that the aromatic base and ribose moiety each move approximately 1.2 A toward each other in the transformation. This study also reveals that, like many other nucleotide binding proteins, coordination of DMB is accompanied by a disorder-order transition in a surface loop. The structure of apo-CobT is also reported.

Capture of a labile substrate by expulsion of water molecules from the active site of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica.,Cheong CG, Escalante-Semerena JC, Rayment I J Biol Chem. 2002 Oct 25;277(43):41120-7. Epub 2002 Jul 5. PMID:12101181[1]

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

See Also

References

  1. Cheong CG, Escalante-Semerena JC, Rayment I. Capture of a labile substrate by expulsion of water molecules from the active site of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase (CobT) from Salmonella enterica. J Biol Chem. 2002 Oct 25;277(43):41120-7. Epub 2002 Jul 5. PMID:12101181 doi:http://dx.doi.org/10.1074/jbc.M203535200

1l4h, resolution 2.10Å

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