Volume 5, Issue 3, Pages (March 1997)

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Volume 5, Issue 3, Pages 337-347 (March 1997) Crystal structure of carboxypeptidase G2, a bacterial enzyme with applications in cancer therapy  Siân Rowsell, Richard A Pauptit, Alec D Tucker, Roger G Melton, David M Blow, Peter Brick  Structure  Volume 5, Issue 3, Pages 337-347 (March 1997) DOI: 10.1016/S0969-2126(97)00191-3

Figure 1 Enzymatic hydrolysis of folate (R1 = OH, R2 = H) or methotrexate (R1 = NH2, R2 = CH3) by CPG2. Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)

Figure 2 Stereo view of the CPG2 subunit α carbon backbone, with some sequence numbering. The catalytic domain is at the top of the figure, with the dimerization domain below. The active-site zinc ions are represented by small circles. (Figure generated using the program MOLSCRIPT [58].) Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)

Figure 3 Ribbon diagram of the CPG2 dimer. One subunit is coloured blue and the other is coloured yellow. The magenta spheres represent the active-site zinc ions. (a) Viewed in the same orientation as Figure 2. (b) Orthogonal view of the CPG2 dimer showing the continuous β sheet across the two subunits forming the dimer interface. (Figure generated using the program MOLSCRIPT [58].) Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)

Figure 4 Overall topology of the carboxypeptidase G2 enzyme. (a) Topological diagram illustrating the secondary structural elements coloured by subdomain. The arrows represent β strands, and the circles represent helices. The secondary structure was assigned on the basis of mainchain hydrogen bonding using the algorithm of Kabsch & Sander [59]. The secondary structural elements belonging to the catalytic domain are coloured pink or grey and those of the dimerization domain are coloured green. The secondary structural elements conserved in LAP, AMP, CPA, CPB and CPT are coloured pink and are numbered. The first helix (helix A) is missing in carboxypeptidases A, B and T. (b) Schematic drawing showing the location of the subdomains in the amino acid sequence, using the same colouring scheme. Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)

Figure 5 Stereo view of the active site of CPG2, viewed in a similar orientation to Figure 2, showing the two zinc ions and their ligands in ball-and-stick representation with atoms in standard colours. The bridging active-site water molecule is indicated as a light blue sphere. Also shown is Glu175, which is likely to promote the attack of the water molecule on the substrate (see text). (Figure generated using the program MOLSCRIPT [58].) Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)

Figure 6 The conserved structural motif in the exopeptidase family. Ribbon diagrams of (a) the catalytic domain of CPG2, (b) AMP, (c) the catalytic domain of LAP and (d) CPA. The secondary structural elements conserved in CPG2, LAP and AMP are coloured purple, non-conserved regions are shown in grey. All except the first helix (helix A) are also conserved in CPA, CPB and CPT. In AMP, this first helix is split into two consecutive helices at the point where the CPG2 helix has a kink caused by a proline (Pro41). (Figure generated using the program MOLSCRIPT [58].) Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)

Figure 7 Stereo view of the active sites of CPG2 (cyan) and AMP (green) when the conserved secondary structural elements are superposed, viewed as in Figure 5. Atoms are shown in standard colours. (Figure generated using the program MOLSCRIPT [58].) Structure 1997 5, 337-347DOI: (10.1016/S0969-2126(97)00191-3)