000199866 001__ 199866
000199866 005__ 20181203023523.0
000199866 0247_ $$2doi$$a10.1007/s00775-014-1108-7
000199866 022__ $$a0949-8257
000199866 02470 $$2ISI$$a000336310000008
000199866 037__ $$aARTICLE
000199866 245__ $$aMolecular dynamics simulations of apocupredoxins: insights into the formation and stabilization of copper sites under entatic control
000199866 260__ $$bSpringer$$c2014$$aNew York
000199866 269__ $$a2014
000199866 300__ $$a11
000199866 336__ $$aJournal Articles
000199866 520__ $$aCupredoxins perform copper-mediated long-range electron transfer (ET) in biological systems. Their copper-binding sites have evolved to force copper ions into ET-competent systems with decreased reorganization energy, increased reduction potential, and a distinct electronic structure compared with those of non-ET-competent copper complexes. The entatic or rack-induced state hypothesis explains these special properties in terms of the strain that the protein matrix exerts on the metal ions. This idea is supported by X-ray structures of apocupredoxins displaying "closed" arrangements of the copper ligands like those observed in the holoproteins; however, it implies completely buried copper-binding atoms, conflicting with the notion that they must be exposed for copper loading. On the other hand, a recent work based on NMR showed that the copper-binding regions of apocupredoxins are flexible in solution. We have explored five cupredoxins in their "closed" apo forms through molecular dynamics simulations. We observed that prearranged ligand conformations are not stable as the X-ray data suggest, although they do form part of the dynamic landscape of the apoproteins. This translates into variable flexibility of the copper-binding regions within a rigid fold, accompanied by fluctuations of the hydrogen bonds around the copper ligands. Major conformations with solvent-exposed copper-binding atoms could allow initial binding of the copper ions. An eventual subsequent incursion to the closed state would result in binding of the remaining ligands, trapping the closed conformation thanks to the additional binding energy and the fastening of noncovalent interactions that make up the rack.
000199866 6531_ $$aCupredoxins
000199866 6531_ $$aFlexibility
000199866 6531_ $$aMetal ion binding
000199866 6531_ $$aCopper
000199866 6531_ $$aEntatic state
000199866 700__ $$uEcole Polytech Fed Lausanne, Sch Life Sci, Lab Biomol Modeling, Lausanne, Switzerland$$aAbriata, Luciano A.
000199866 700__ $$uUniv Nacl Rosario, Inst Biol Mol & Celular Rosario IBR, CONICET UNR, RA-2000 Rosario, Santa Fe, Argentina$$aVila, Alejandro J.
000199866 700__ $$g182443$$uEcole Polytech Fed Lausanne, Sch Life Sci, Lab Biomol Modeling, Lausanne, Switzerland$$aDal Peraro, Matteo$$0243887
000199866 773__ $$j19$$tJournal Of Biological Inorganic Chemistry$$k4-5$$q565-575
000199866 909C0 $$xU11830$$0252070$$pUPDALPE
000199866 909CO $$pSV$$particle$$ooai:infoscience.tind.io:199866
000199866 937__ $$aEPFL-ARTICLE-199866
000199866 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000199866 980__ $$aARTICLE