Banca de DEFESA: EMMANUEL DUARTE BARBOSA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : EMMANUEL DUARTE BARBOSA
DATA : 29/07/2016
HORA: 14:00
LOCAL: Sala Carl Peter von Dietrich - Depto. de Bioquímica - CB/UFRN
TÍTULO:

QUANTUM BIOCHEMISTRY DESCRIPTION OF POCKET ÍON INTERACTION ZN²⁺  IN HUMAN ALAD ENZYME

PALAVRAS-CHAVES:

ALAD, binding energies, MFCC, DFT.

PÁGINAS: 51
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

The enzyme Delta Aminolevulinic Dehydratase (ALAD) is a cytosolic metalloproteinase essential in several biological processes since it participates in the second step in porphobilinogen formation pathway, a tetrapyrrolic precursor of heme and chlorophyll. This enzyme is very sensitive to heavy metals and has traditionally been used as a biomarker in lead poisoning. Its inhibition occurs when these heavy metals are replaced inside the metal binding site. In human ALAD, Zinc (Zn²⁺) functionally occupies this site and it is essential for coordination of two chains of aminolevulinic acid for the enzymatic catalysis. Although many in vitro, in vivo and in silico works have already demonstrated the importance of Zn at that site, to the best of our knowledge, there isn’t any studies on literature based on quantum approach in order to elucidate this interactions in more details. Therefore, the aim of the present study was to analyse energetically these interactions between zinc and ALAD with greater accuracy using the method of Molecular fractionation with conjugated caps (MFCC) by quantifying amino acid residues’ energy positioned at 8.5 Å of distance with the ligand centroid. It were identified a total of 30 residues with a wide range of energy values. The residues with significant (atractition or repulsion) values and functionally related to enzymatic activity were: Lys199,

Lys120, Cys122, Cys124 and Cys132; and those that demonstrated relevance to the ion permanence inside the binding site were: Asp169, Gly130, Gly133, Asp120 and Ser168. Thus, it could be concluded that in addition to the nucleophilic groups (thiolates groups) from Cys122, Cys124 and Cys132, others residues such as Asp169, Asp120 and Ser168 are fundamental in the catalytic pocket composition, since they showed high attractive interaction energy with Zn²⁺ ion.

 

MEMBROS DA BANCA:
Externo à Instituição - MARIALVA SINIGAGLIA - UFRGS
Interno - 1352009 - UMBERTO LAINO FULCO
Presidente - 1674709 - VIVIANE SOUZA DO AMARAL