## 3 The Rubisco's Secondary, Tertiary and Quaternary Structure  
Due to the wide range of protein structures solved by X-ray crystallography and the availability of genomic and metabolomic data, four different Rubisco molecular isoforms have been identified in nature that essentially differ in the number of subunits and their arrangement within the macromolecular complex (Figure 1) [13]. Isoforms I and II, whose structural features are discussed in this section, play a central role in carbon fixation via the CBB cycle. The phylogenetic distribution of form I Rubisco encompasses all higher plants, red and brown algae, cyanobacteria and most chemoautotrophic bacteria while form II is found in photosynthetic bacteria and several methanogenic Archaea. Mentioning briefly the remaining isoform of Rubisco proteins, form III Rubisco is found exclusively in Archaea and isoform IV (also named Rubisco-like protein, RLP) is found in both Bacteria and Archaea where it may have a role in sulfur metabolism. This section analyzes the structural features of Rubisco proteins to provide a molecular basis for subsequent description of the carboxylase reaction mechanism. A detailed overview of the Rubisco's structure and function can be found in the review published by [PERSON] and [PERSON] in 2008 covering structures deposited to the PDB (Protein Data Bank) archive over approximately a 20-year period (including Rubisco-like proteins) [13]. Since 2008, several additional Rubisco structures have been solved by X-ray as, for example, the crystal structure of Rubisco from _Pisunt sativum_, [14]_Galderia sulphuraria_, [15]_Rhodospseudomonas palustris_[16] and _Arabidopsis thaliana_[17]. The pioneering work published by [PERSON] et al., in 1987 [18] describes Rubisco from _Nicotidiana tabacum_ (form I Rubisco) as a globular protein, barrel-shaped (\"a leg 105 A along the 4-fold axis and 132 A in diameter at the widest point of the leg\"), showing a L\({}_{8}\)S\({}_{8}\) quaternary structure where L denotes the \"large\" catalytic subunit and S denotes the \"small\" subunit (L: 52.9 kDa; S: 14.8 kDa). The eight L subunits are arranged as a toroid around a \(z\)-axis of four-fold symmetry. Along this axis a solvent channel transverses the molecular complex. The molecular symmetry of the L\({}_{8}\)S\({}_{8}\) hexa-decamer of Rubisco from spinach is shown in Figure 1a [19]. Figure 1a is a view along the four-fold axis, while Figure 1b shows the protein viewed along one of the two-fold axes. In Figure 1b the two large subunits of the front-facing L\({}_{2}\) dimer are shown in yellow and blue color. The polypeptide chains of each L\({}_{2}\) dimer assume an antiparallel arrangement so that, the N-terminal domain of the yellow L subunit is close to the C-terminal domain of the blue L subunit. Figure 1: (**a**) Schematic drawing of Form I Rubisco from spinach showing the spatial arrangement of the L\({}_{8}\)S\({}_{8}\) hexa-decamer view along the four-fold axis. The L subunits appearing in the figure are represented in yellow and blue. The figure also evidences the S subunits (represented in orange) delimiting the solvent channel; (**b**) schematic drawing of the Rubisco from spinach, view along one of the two-fold axes; (**c**) Form II Rubisco from _Rhodospirillum rubrum_ showing the two-fold symmetry of the L2 dimer. The substrate mimic 2-carboxy-D-arabinitol 1,5-bisphosphate (2 CABP), displayed as red spheres (Figure from ref. [19], adapted and used by permission of Elsevier (copyright © 2003). Figure 1a,b also show the arrangement of the S subunits (represented in orange) clustered around the four-fold axis. Figure 1c represents a schematic drawing of the quaternary structure of type II Rubisco from _Rhodospirillum rubrum_ consisting of a L\({}_{2}\) dimer [19]. The secondary structure elements (\(\alpha\)-helices, \(\beta\)-strands and loops) of the polypeptide chain of Rubisco from spinach are shown in the connectivity diagram reported in Scheme S2 [20].