Carvalho, AL, Dias FMV, Prates JAM, Nagy T, Gilbert HJ, Davies GJ, Ferreira LMA, Romao MJ, Fontes C.
2003.
Cellulosome assembly revealed by the crystal structure of the cohesin-dockerin complex. Proceedings of the National Academy of Sciences of the United States of America. 100:13809-13814., Number 24
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Mahro, M, Coelho C, Trincao J, Rodrigues D, Terao M, Garattini E, Saggu M, Lendzian F, Hildebrandt P, Romao MJ, Leimkuehler S.
2011.
Characterization and Crystallization of Mouse Aldehyde Oxidase 3: From Mouse Liver to Escherichia coli Heterologous Protein Expression. Drug Metabolism and Disposition. 39:1939-1945., Number 10
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Seixas, JD, Mukhopadhyay A, Santos-Silva T, Otterbein LE, Gallo DJ, Rodrigues SS, Guerreiro BH, Goncalves AML, Penacho N, Marques AR, Coelho AC, Reis PM, Romao MJ, Romao CC.
2013.
Characterization of a versatile organometallic pro-drug (CORM) for experimental CO based therapeutics. Dalton Transactions. 42:5985-5998., Number 17
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Kladova, AV, Gavel YO, Mukhopaadhyay A, Boer DR, Teixeira S, Shnyrov VL, Moura I, Moura JJG, Romao MJ, Trincao J, Bursakov SA.
2009.
Cobalt-, zinc- and iron-bound forms of adenylate kinase (AK) from the sulfate-reducing bacterium Desulfovibrio gigas: purification, crystallization and preliminary X-ray diffraction analysis. Acta Crystallographica Section F-Structural Biology and Crystallization Communications. 65:926-929.
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Seixas, JD, Santos MFA, Mukhopadhyay A, Coelho AC, Reis PM, Veiros LF, Marques AR, Penacho N, Goncalves AML, Romao MJ, Bernardes GJL, Santos-Silva T, Romao CC.
2015.
A contribution to the rational design of Ru(CO)(3)Cl2L complexes for in vivo delivery of CO. Dalton Transactions. 44:5058-5075., Number 11
AbstractA few ruthenium based metal carbonyl complexes, e.g. CORM-2 and CORM-3, have therapeutic activity attributed to their ability to deliver CO to biological targets. In this work, a series of related complexes with the formula [Ru(CO)(3)Cl2L] (L = DMSO (3), L-H3CSO(CH2)(2)CH(NH2)CO2H) (6a); D,L-H3CSO(CH2)(2)CH-(NH2)CO2H (6b); 3-NC5H4(CH2)(2)SO3.Na (7); 4-NC5H4(CH2)(2)SO3Na (8); PTA (9); DAPTA (10); H3CS-(CH2)(2)CH(OH) CO2H (11); CNCMe2CO2Me (12); CNCMeEtCO2Me (13); CN(c-C3H4)CO2Et) (14)) were designed, synthesized and studied. The effects of L on their stability, CO release profile, cytotoxicity and anti-inflammatory properties are described. The stability in aqueous solution depends on the nature of L as shown using HPLC and LC-MS studies. The isocyanide derivatives are the least stable complexes, and the S-bound methionine oxide derivative is the more stable one. The complexes do not release CO gas to the headspace, but release CO2 instead. X-ray diffraction of crystals of the model protein Hen Egg White Lysozyme soaked with 6b (4UWN) and 8 (4UWV) shows the addition of Ru-II(CO)(H2O)(4) at the His15 binding site. Soakings with 7 (4UWU) produced the metallacarboxylate [Ru(COOH)(CO)(H2O)(3)](+) bound to the His15 site. The aqueous chemistry of these complexes is governed by the water-gas shift reaction initiated with the nucleophilic attack of HO- on coordinated CO. DFT calculations show this addition to be essentially barrierless. The complexes have low cytotoxicity and low hemolytic indices. Following i.v. administration of CORM-3, the in vivo bio-distribution of CO differs from that obtained with CO inhalation or with heme oxygenase stimulation. A mechanism for CO transport and delivery from these complexes is proposed.
Gomes, AS, Trovão F, Andrade Pinheiro B, Freire F, Gomes S, Oliveira C, Domingues L, Romão MJ, Saraiva L, Carvalho AL.
2018.
The Crystal Structure of the R280K Mutant of Human p53 Explains the Loss of DNA Binding. International Journal of Molecular Sciences. 19, Number 4}, ARTICLE NUMBER = {1184
AbstractThe p53 tumor suppressor is widely found to be mutated in human cancer. This protein is regarded as a molecular hub regulating different cell responses, namely cell death. Compelling data have demonstrated that the impairment of p53 activity correlates with tumor development and maintenance. For these reasons, the reactivation of p53 function is regarded as a promising strategy to halt cancer. In the present work, the recombinant mutant p53R280K DNA binding domain (DBD) was produced for the first time, and its crystal structure was determined in the absence of DNA to a resolution of 2.0 Å. The solved structure contains four molecules in the asymmetric unit, four zinc(II) ions, and 336 water molecules. The structure was compared with the wild-type p53 DBD structure, isolated and in complex with DNA. These comparisons contributed to a deeper understanding of the mutant p53R280K structure, as well as the loss of DNA binding related to halted transcriptional activity. The structural information derived may also contribute to the rational design of mutant p53 reactivating molecules with potential application in cancer treatment.
Mukhopadhyay, A, Kladova AV, Bursakov SA, Gavel YO, Calvete JJ, Shnyrov VL, Moura I, Moura JJG, Romao MJ, Trincao J.
2011.
Crystal structure of the zinc-, cobalt-, and iron-containing adenylate kinase from Desulfovibrio gigas: a novel metal-containing adenylate kinase from Gram-negative bacteria. Journal of Biological Inorganic Chemistry. 16:51-61., Number 1
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Cunha, CA, Macieira S, Dias JM, Almeida G, Goncalves LL, Costa C, Lampreia J, Huber R, Moura JJG, Moura I, Romao MJ.
2003.
Cytochrome c nitrite reductase from Desulfovibrio desulfuricans ATCC 27774 - The relevance of the two calcium sites in the structure of the catalytic subunit (NrfA). Journal of Biological Chemistry. 278:17455-17465., Number 19
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