000151199 001__ 151199
000151199 005__ 20181203021957.0
000151199 022__ $$a0961-8368
000151199 02470 $$2PMID$$a17660248
000151199 0247_ $$2doi$$a10.1110/ps.072982707
000151199 037__ $$aARTICLE
000151199 245__ $$aThe crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria
000151199 269__ $$a2007
000151199 260__ $$c2007
000151199 336__ $$aJournal Articles
000151199 520__ $$aMycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Structural Genomics initiative on conserved hypothetical proteins in pathogenic mycobacteria, we have determined the structure of ML2640c in two distinct crystal forms. As expected, ML2640c has a typical MTase core domain and binds the methyl donor substrate AdoMet in a manner consistent with other known members of this structural family. The putative acceptor substrate-binding site of ML2640c is a large internal cavity, mostly lined by aromatic and aliphatic side-chain residues, suggesting that a lipid-like molecule might be targeted for catalysis. A flap segment (residues 222-256), which isolates the binding site from the bulk solvent and is highly mobile in the crystal structures, could serve as a gateway to allow substrate entry and product release. The multiple sequence alignment of ML2640c-like proteins revealed that the central alpha/beta core and the AdoMet-binding site are very well conserved within the family. However, the amino acid positions defining the binding site for the acceptor substrate display a higher variability, suggestive of distinct acceptor substrate specificities. The ML2640c crystal structures offer the first structural glimpses at this important family of mycobacterial proteins and lend strong support to their functional assignment as AdoMet-dependent methyltransferases.
000151199 700__ $$aGraña, Martin
000151199 700__ $$aHaouz, Ahmed
000151199 700__ $$aBuschiazzo, Alejandro
000151199 700__ $$aMiras, Isabelle
000151199 700__ $$aWehenkel, Annemarie
000151199 700__ $$aBondet, Vincent
000151199 700__ $$aShepard, William
000151199 700__ $$aSchaeffer, Francis
000151199 700__ $$0243892$$aCole, Stewart T$$g177247
000151199 700__ $$aAlzari, Pedro M
000151199 773__ $$j16$$k9$$q1896-904$$tProtein science : a publication of the Protein Society
000151199 909C0 $$0252302$$pUPCOL$$xU11742
000151199 909CO $$ooai:infoscience.tind.io:151199$$pSV$$particle
000151199 937__ $$aEPFL-ARTICLE-151199
000151199 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000151199 980__ $$aARTICLE