4jem: Difference between revisions
New page: '''Unreleased structure''' The entry 4jem is ON HOLD Authors: Sikowitz, M.D., Cooper, L.E., Begley, T.P., Kaminski, P.A., Ealick, S.E. Description: Crystal structure of MilB complexed ... |
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The | ==Crystal structure of MilB complexed with cytidine 5'-monophosphate== | ||
<StructureSection load='4jem' size='340' side='right'caption='[[4jem]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jem]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_rimofaciens Streptomyces rimofaciens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JEM 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]] 1.553Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C5P:CYTIDINE-5-MONOPHOSPHATE'>C5P</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=4jem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jem OCA], [https://pdbe.org/4jem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jem RCSB], [https://www.ebi.ac.uk/pdbsum/4jem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jem ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/B4Y381_9ACTN B4Y381_9ACTN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
MilB is a CMP hydrolase involved in the early steps of biosynthesis of the antifungal compound mildiomycin. An enzyme from the bacimethrin biosynthetic pathway, BcmB, is closely related to MilB in both sequence and function. These two enzymes belong to the nucleoside 2'-deoxyribosyltransferase (NDT) superfamily. NDTs catalyze N-glycosidic bond cleavage of 2'-deoxynucleosides via a covalent 2-deoxyribosyl-enzyme intermediate. Conservation of key active site residues suggests that members of the NDT superfamily share a common mechanism; however, the enzymes differ in their substrate preferences. Substrates vary in the type of nucleobase, the presence or absence of a 2'-hydroxyl group, and the presence or absence of a 5'-phosphate group. We have determined the structures of MilB and BcmB and compared them to previously determined structures of NDT superfamily members. The comparisons reveal how these enzymes differentiate between ribosyl and deoxyribosyl nucleotides or nucleosides and among different nucleobases. The 1.6 A structure of the MilB-CMP complex reveals an active site feature that is not obvious from comparisons of sequence alone. MilB and BcmB that prefer substrates containing 2'-ribosyl groups have a phenylalanine positioned in the active site, whereas NDT family members with a preference for 2'-deoxyribosyl groups have a tyrosine residue. Further studies show that the phenylalanine is critical for the specificity of MilB and BcmB toward CMP, and mutation of this phenylalanine residue to tyrosine results in a 1000-fold reversal of substrate specificity from CMP to dCMP. | |||
Reversal of the substrate specificity of CMP N-glycosidase to dCMP.,Sikowitz MD, Cooper LE, Begley TP, Kaminski PA, Ealick SE Biochemistry. 2013 Jun 11;52(23):4037-47. doi: 10.1021/bi400316p. Epub 2013 May, 28. PMID:23659472<ref>PMID:23659472</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4jem" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces rimofaciens]] | |||
[[Category: Begley TP]] | |||
[[Category: Cooper LE]] | |||
[[Category: Ealick SE]] | |||
[[Category: Kaminski PA]] | |||
[[Category: Sikowitz MD]] | |||
Latest revision as of 18:41, 20 September 2023
Crystal structure of MilB complexed with cytidine 5'-monophosphateCrystal structure of MilB complexed with cytidine 5'-monophosphate
Structural highlights
FunctionPublication Abstract from PubMedMilB is a CMP hydrolase involved in the early steps of biosynthesis of the antifungal compound mildiomycin. An enzyme from the bacimethrin biosynthetic pathway, BcmB, is closely related to MilB in both sequence and function. These two enzymes belong to the nucleoside 2'-deoxyribosyltransferase (NDT) superfamily. NDTs catalyze N-glycosidic bond cleavage of 2'-deoxynucleosides via a covalent 2-deoxyribosyl-enzyme intermediate. Conservation of key active site residues suggests that members of the NDT superfamily share a common mechanism; however, the enzymes differ in their substrate preferences. Substrates vary in the type of nucleobase, the presence or absence of a 2'-hydroxyl group, and the presence or absence of a 5'-phosphate group. We have determined the structures of MilB and BcmB and compared them to previously determined structures of NDT superfamily members. The comparisons reveal how these enzymes differentiate between ribosyl and deoxyribosyl nucleotides or nucleosides and among different nucleobases. The 1.6 A structure of the MilB-CMP complex reveals an active site feature that is not obvious from comparisons of sequence alone. MilB and BcmB that prefer substrates containing 2'-ribosyl groups have a phenylalanine positioned in the active site, whereas NDT family members with a preference for 2'-deoxyribosyl groups have a tyrosine residue. Further studies show that the phenylalanine is critical for the specificity of MilB and BcmB toward CMP, and mutation of this phenylalanine residue to tyrosine results in a 1000-fold reversal of substrate specificity from CMP to dCMP. Reversal of the substrate specificity of CMP N-glycosidase to dCMP.,Sikowitz MD, Cooper LE, Begley TP, Kaminski PA, Ealick SE Biochemistry. 2013 Jun 11;52(23):4037-47. doi: 10.1021/bi400316p. Epub 2013 May, 28. PMID:23659472[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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