| http://purl.uniprot.org/citations/21918843 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21918843 | http://www.w3.org/2000/01/rdf-schema#comment | "In this density functional theory study, reaction mechanisms of a co-catalytic binuclear metal center (Zn1-Zn2) containing enzyme leucine aminopeptidase for two different metal bridging nucleophiles (H(2)O and -OH) have been investigated. In addition, the effects of the substrate (L-leucine-p-nitroanilide → L-leucyl-p-anisidine) and metal (Zn1 → Mg and Zn2 → Co, i.e., Mg1-Zn2 and Mg1-Co2 variants) substitutions on the energetics of the mechanism have been investigated. The general acid/base mechanism utilizing a bicarbonate ion followed by this enzyme is divided into two steps: (1) the formation of the gem-diolate intermediate, and (2) the cleavage of the peptide bond. With the computed barrier of 17.8 kcal/mol, the mechanism utilizing a hydroxyl nucleophile was found to be in excellent agreement with the experimentally measured barrier of 18.7 kcal/mol. The rate-limiting step for reaction with L-leucine-p-nitroanilide is the cleavage of the peptide bond with a barrier of 17.8 kcal/mol. However, for L-leucyl-p-anisidine all steps of the mechanism were found to occur with similar barriers (18.0-19.0 kcal/mol). For the metallovariants, cleavage of the peptide bond occurs in the rate-limiting step with barriers of 17.8, 18.0, and 24.2 kcal/mol for the Zn1-Zn2, Mg1-Zn2, and Mg1-Co2 enzymes, respectively. The nature of the metal ion was found to affect only the creation of the gem-diolate intermediate, and after that all three enzymes follow essentially the same energetics. The results reported in this study have elucidated specific roles of both metal centers, the nucleophile, indirect ligands, and substrates in the catalytic functioning of this important class of binuclear metallopeptidases."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00775-011-0843-2"xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/author | "Zhang T."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/author | "Zhu X."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/author | "Ozbil M."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/author | "Barman A."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/author | "Prabhakar R."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/name | "J Biol Inorg Chem"xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/pages | "209-222"xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/title | "Mechanism of peptide hydrolysis by co-catalytic metal centers containing leucine aminopeptidase enzyme: a DFT approach."xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://purl.uniprot.org/core/volume | "17"xsd:string |
| http://purl.uniprot.org/citations/21918843 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21918843 |
| http://purl.uniprot.org/citations/21918843 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21918843 |
| http://purl.uniprot.org/uniprot/#_P00727-mappedCitation-21918843 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21918843 |
| http://purl.uniprot.org/uniprot/P00727 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/21918843 |