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Biochim Biophys Acta. 2016 May;1857(5):531-538. doi: 10.1016/j.bbabio.2015.10.001. Epub 2015 Oct 9.

Structural principles for computational and de novo design of 4Fe-4S metalloproteins.

Author information

1
Department of Biochemistry and Molecular Biology and the Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Rutgers University, 679 Hoes Lane West, Piscataway, NJ, 08854, USA. Electronic address: nanda@cabm.rutgers.edu.
2
Department of Biochemistry and Molecular Biology and the Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Rutgers University, 679 Hoes Lane West, Piscataway, NJ, 08854, USA.
3
Department of Chemistry and the Center for Integrated Proteomics Research, Rutgers University, 174 Frelinghuysen Rd, Piscataway, NJ 08854, USA.
4
Bioenergetics and Protein Design Laboratory, Migal - Galilee Research Institute, South Industrial Zone, Kiryat Shmona 11016, Israel.

Abstract

Iron-sulfur centers in metalloproteins can access multiple oxidation states over a broad range of potentials, allowing them to participate in a variety of electron transfer reactions and serving as catalysts for high-energy redox processes. The nitrogenase FeMoCO cluster converts di-nitrogen to ammonia in an eight-electron transfer step. The 2(Fe4S4) containing bacterial ferredoxin is an evolutionarily ancient metalloprotein fold and is thought to be a primordial progenitor of extant oxidoreductases. Controlling chemical transformations mediated by iron-sulfur centers such as nitrogen fixation, hydrogen production as well as electron transfer reactions involved in photosynthesis are of tremendous importance for sustainable chemistry and energy production initiatives. As such, there is significant interest in the design of iron-sulfur proteins as minimal models to gain fundamental understanding of complex natural systems and as lead-molecules for industrial and energy applications. Herein, we discuss salient structural characteristics of natural iron-sulfur proteins and how they guide principles for design. Model structures of past designs are analyzed in the context of these principles and potential directions for enhanced designs are presented, and new areas of iron-sulfur protein design are proposed. This article is part of a Special issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, protein networks, edited by Ronald L. Koder and J.L Ross Anderson.

KEYWORDS:

Iron-sulfur; Metalloprotein; Oxidoreductase; Protein design; Symmetry

PMID:
26449207
PMCID:
PMC5389887
DOI:
10.1016/j.bbabio.2015.10.001
[Indexed for MEDLINE]
Free PMC Article

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