Volume 3, Issue 6, Pages 541-549 (June 1995) Structure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed β-propeller  J Li, P Brick, MC O'Hare, T Skarzynski, LF Lloyd, VA Curry, IM Clark, HF Bigg, BL Hazleman, TE Cawston, DM Blow  Structure  Volume 3, Issue 6, Pages 541-549 (June 1995) DOI: 10.1016/S0969-2126(01)00188-5

Figure 1 Chemical structure of the CIC inhibitor. The material used was a racemic mixture of R-  and S-configurations at the Cα of the leucine moiety. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 2 Orthogonal views of the collagenase molecule in complex with the CIC inhibitor. (a) View down the fourfold axis of the haemopexin-like domain. The N-terminal catalytic domain (residues 100–260) is at the top of the figure and includes the inhibitor displayed with yellow carbon atoms. The three histidine residues (His218, His222 and His228) that coordinate the catalytic zinc ion are drawn with green carbon atoms and both the catalytic and the structural zinc ions are shown as magenta spheres. The catalytic domain also contains three calcium ions (red spheres). The haemopexin-like domain (residues 278–466) contains one calcium ion on the fourfold axis at the N-terminal end of the β-strands. The outermost (fourth) β-strand is interrupted in sheets 2 and 3 (numbering sheets from 1 at the top left clockwise to 4 at the bottom left) of the β-propeller, and is shown as two separate sections of β-structure. A helical turn directly follows this fourth β-strand in the first three of the four sheets which make up this domain. The disulphide bond, shown in yellow, links the two ends of the haemopexin-like domain. (b) A view of the molecule perpendicular to the fourfold axis showing the exposed proline-rich peptide linking the two domains. (Figures generated using the programs MOLSCRIPT [39] and Raster3D [40].) Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 3 Stereo diagram showing a Cα trace of the C-terminal haemopexin-like domain (residues 260–466) with numbering at approximately 10-residue intervals. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 4 Schematic representation of the antiparallel β-sheets of the haemopexin-like domain. Each part of the figure represents a pair of sheets which are approximately in the same plane. (a) Sheets 1 and 3. (b) Sheets 2 and 4. The approximate fourfold symmetry axis of the domain is vertical. In each sheet, the parts of the structure which conform strictly to the Kabsch and Sander [41] definition of β-sheet structure are outlined. Parts (a) and (b) represent roughly perpendicular views. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 4 Schematic representation of the antiparallel β-sheets of the haemopexin-like domain. Each part of the figure represents a pair of sheets which are approximately in the same plane. (a) Sheets 1 and 3. (b) Sheets 2 and 4. The approximate fourfold symmetry axis of the domain is vertical. In each sheet, the parts of the structure which conform strictly to the Kabsch and Sander [41] definition of β-sheet structure are outlined. Parts (a) and (b) represent roughly perpendicular views. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 5 Section of the electron-density map of the haemopexin-like domain comparable to the schematic diagram in Figure 4a. The map is contoured at 1σ and was calculated using coefficients (3Fo–2Fc) with phases obtained from the final model. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 6 Comparison of sequences in the haemopexin-like domains of MMPs and human haemopexin. Each horizontal block (set of four sequences) represents one sheet of the domain. The sequence of porcine MMP-1, and the sequences of both corresponding domains of human haemopexin are given. Underlining indicates the strands of β-sheet in porcine MMP-1, assigned according to the definition of Kabsch and Sander [41]. A consensus sequence derived by comparing 10 MMP types is given above the MMP-1 sequence. An amino acid is part of the consensus if it exists in 6 or more of the 10 MMP sequences and is shown in italics if present in all 10. Following Hunt et al. [16], the four sheets have been aligned to show the significant homologies between them, and boxes indicate where the MMP consensus agrees with both domains of human haemopexin. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)

Figure 7 Section of the electron-density map viewed down the fourfold axis of the haemopexin-like domain. This view includes a water molecule on the axis, the four alanine residues that pack together tightly in strand 1 and the Phe-Phe sequence present in strand 2 of each of the four sheets. The map is contoured at 1σ and was calculated using coefficients (3Fo–2Fc) with phases obtained from the final model. Structure 1995 3, 541-549DOI: (10.1016/S0969-2126(01)00188-5)