抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Two major energy-related problems confront the world in the
next 50 years. First, increased worldwide competition for
gradually depleting fossil fuel reserves (derived from past
photosynthesis) will lead to higher costs, both monetarily and politically. Second, atmospheric CO_2 levels are at their highest recorded level since records began. Further increases are predicted to produce large and uncontrollable impacts on the world climate. These projected impacts extend beyond climate to ocean acidification, because the ocean is a major sink for atmospheric CO2.1 Providing a future energy supply that is secure and CO_2-neutral will require switching to nonfossil energy sources such as wind, solar, nuclear, and geothermal energy and developing methods for transforming the energy produced by these new sources into forms that can be stored, transported, and used upon demand.

Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO2 Fixation

This article sets out to review the chemistry relating to the synthesis of structural and functional analogues of the three classes of hydrogenases. This chemistry has grown explosively over the last 10 or so years since the first X-ray structures of [NiFe]- and [FeFe]-hydrogenase systems were published. There are now some 400 papers covering structural and functional aspects, with the majority of these associated with the di-iron system. As much emphasized in earlier papers

Structural and functional analogues of the active sites of the [Fe]-, [NiFe]-, and [FeFe]-hydrogenases.

Artificial photosynthesis: molecular systems for catalytic water oxidation.

Interconversion of water and hydrogen in unitized regenerative fuel cells is a promising energy storage framework for smoothing out the temporal fluctuations of solar and wind power. However, replacement of presently available platinum catalysts by lower-cost and more abundant materials is a requisite for this technology to become economically viable. Here, we show that the covalent attachment of a nickel bisdiphosphine–based mimic of the active site of hydrogenase enzymes onto multiwalled carbon nanotubes results in a high–surface area cathode material with high catalytic activity under the strongly acidic conditions required in proton exchange membrane technology. Hydrogen evolves from aqueous sulfuric acid solution with very low overvoltages (20 millivolts), and the catalyst exhibits exceptional stability (more than 100,000 turnovers). The same catalyst is also very efficient for hydrogen oxidation in this environment, exhibiting current densities similar to those observed for hydrogenase-based materials.

/pdf/from-hydrogenases-to-noble-metal-free-catalytic-fotyu2q2uf.pdf

From hydrogenases to noble metal-free catalytic nanomaterials for H2 production and uptake.

Hydrogenases are enzymes catalyzing the reversible heterolytic splitting of molecular hydrogen. Despite extensive investigations of this class of enzymes its catalytic mechanism is not yet well understood. In this paper spectroscopic investigations of the active site of [FeFe] hydrogenase are presented. The so-called H-cluster consists of a bi-nuclear catalytically active subcluster connected to a [4Fe4S] ferredoxin-like unit via a Cys–thiol bridge. An important feature of the H-cluster is that both irons in the bi-nuclear subcluster are coordinated by CN and CO ligands. The bi-nuclear site also carries a dithiol bridge, whose central atom has not yet been identified. Nitrogen and oxygen are the most probable candidates from a mechanistic point of view. Here we present a study of the 14N nuclear quadrupole and hyperfine interactions of the active oxidized state of the H-cluster using advanced EPR methods. In total three 14N nuclei with quadrupole couplings of 0.95 MHz, 0.35 MHz and 1.23 MHz were detected using hyperfine sublevel correlation spectroscopy (HYSCORE). The assignment of the signals is based on their 14N quadrupole couplings in combination with DFT calculations. One signal is assigned to the CN ligand of the distal iron, one to a Lys side chain nitrogen and one to the putative nitrogen of the dithiol bridge. Hence, these results provide the first experimental evidence for a di-(thiomethyl)amine ligand (–S–CH2–NH–CH2–S–) in the bi-nuclear subcluster. This finding is important for understanding the mechanism of [FeFe] hydrogenases, since the nitrogen is likely to act as an internal base facilitating the heterolytic splitting/formation of H2.

https://www.rsc.org/suppdata/CP/b9/b905841a/b905841a.pdf

(14)N HYSCORE investigation of the H-cluster of [FeFe] hydrogenase: evidence for a nitrogen in the dithiol bridge.

Cytochrome P450 enzymes activate oxygen at heme iron centers to oxidize relatively inert substrate carbon-hydrogen bonds. Cysteine thiolate coordination to iron is posited to increase the pK(a) (where K(a) is the acid dissociation constant) of compound II, an iron(IV)hydroxide complex, correspondingly lowering the one-electron reduction potential of compound I, the active catalytic intermediate, and decreasing the driving force for deleterious auto-oxidation of tyrosine and tryptophan residues in the enzyme's framework. Here, we report on the preparation of an iron(IV)hydroxide complex in a P450 enzyme (CYP158) in ≥90% yield. Using rapid mixing technologies in conjunction with Mossbauer, ultraviolet/visible, and x-ray absorption spectroscopies, we determine a pK(a) value for this compound of 11.9. Marcus theory analysis indicates that this elevated pK(a) results in a >10,000-fold reduction in the rate constant for oxidations of the protein framework, making these processes noncompetitive with substrate oxidation.

/pdf/iron-iv-hydroxide-pka-and-the-role-of-thiolate-ligation-in-c-59ikexsvkw.pdf

Iron(IV)hydroxide pKa and the Role of Thiolate Ligation in C–H Bond Activation by Cytochrome P450

Identification and Characterization of the “Super-Reduced” State of the H-Cluster in [FeFe] Hydrogenase: A New Building Block for the Catalytic Cycle?†

The active site of the (57)Fe-enriched [FeFe]-hydrogenase (i.e., the "H-cluster") from Desulfovibrio desulfuricans has been examined using advanced pulse EPR methods at X- and Q-band frequencies. For both the active oxidized state (H(ox)) and the CO inhibited form (H(ox)-CO) all six (57)Fe hyperfine couplings were detected. The analysis shows that the apparent spin density extends over the whole H-cluster. The investigations revealed different hyperfine couplings of all six (57)Fe nuclei in the H-cluster of the H(ox)-CO state. Four large 57Fe hyperfine couplings in the range 20-40 MHz were found (using pulse ENDOR and TRIPLE methods) and were assigned to the [4Fe-4S](H) (cubane) subcluster. Two weak (57)Fe hyperfine couplings below 5 MHz were identified using Q-band HYSCORE spectroscopy and were assigned to the [2Fe](H) subcluster. For the H(ox) state only two different 57Fe hyperfine couplings in the range 10-13 MHz were detected using pulse ENDOR. An (57)Fe line broadening analysis of the X-band CW EPR spectrum indicated, however, that all six (57)Fe nuclei in the H-cluster are contributing to the hyperfine pattern. It is concluded that in both states the binuclear subcluster [2Fe](H) assumes a [Fe(I)Fe(II)] redox configuration where the paramagnetic Fe(I) atom is attached to the [4Fe-4S](H) subcluster. The (57)Fe hyperfine interactions of the formally diamagnetic [4Fe-4S](H) are due to an exchange interaction between the two subclusters as has been discussed earlier by Popescu and Munck [Popescu, C.V.; Munck, E., J. Am. Chem. Soc. 1999, 121, 7877-7884]. This exchange coupling is strongly enhanced by binding of the extrinsic CO ligand. Binding of the dihydrogen substrate may induce a similar effect, and it is therefore proposed that the observed modulation of the electronic structure by the changing ligand surrounding plays an important role in the catalytic mechanism of [FeFe]-hydrogenase.

The electronic structure of the H-cluster in the [FeFe]-hydrogenase from Desulfovibrio desulfuricans: a Q-band 57Fe-ENDOR and HYSCORE study.

Convincing evidence for the presence of a nitrogen atom in the dithiolate bridge of the active site of native [FeFe] hydrogenases (B) is provided by a spectroscopic, electrochemical, and theoretica ...

Alexey Silakov

Papers

(14)N HYSCORE investigation of the H-cluster of [FeFe] hydrogenase: evidence for a nitrogen in the dithiol bridge.

Iron(IV)hydroxide pKa and the Role of Thiolate Ligation in C–H Bond Activation by Cytochrome P450

Identification and Characterization of the “Super-Reduced” State of the H-Cluster in [FeFe] Hydrogenase: A New Building Block for the Catalytic Cycle?†

The electronic structure of the H-cluster in the [FeFe]-hydrogenase from Desulfovibrio desulfuricans: a Q-band 57Fe-ENDOR and HYSCORE study.

A Model of the [FeFe] Hydrogenase Active Site with a Biologically Relevant Azadithiolate Bridge: A Spectroscopic and Theoretical Investigation