The domain interface. The second phenylalanine side chain sticks into the
The domain interface. The second phenylalanine side chain sticks in to the core of C2, and histidine side chain is inside the interface. A third conserved motif, KX(DE)L(DE)X5(RK) [Fig. (E)], is distinguished by a number of ionizable side chains. It adopts helical structure at the domain interface in PTEN, forming contacts using the Nterminus of theHaynie and XuePROTEIN SCIENCE VOL 24:874either no domain is situated downstream of PTPC2, as in PTEN, or PTPC2 is followed by J, SH2 or PTB, as in GAK and tensins.2 PTPC2 inside the aquatic organisms (triangles) is much less simple than in the terrestrial animals. The arrow indicates a feasible exception. PTENlike, this Helobdella robusta protein consists of just PTPC2. The pI of human PTEN is eight.05 (star). Two, evaluation on the signature motif [Fig. (A)] suggests the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24638984 importance of an acidic side chain in the active site. In human TNS3, for example, the sequence is WPE. . .IHCRGGKGRI. The Glu side chain, though distant in sequence in the Cys nucleophile, may function as a general acid within the phosphatase reaction mechanism.30 This residue is Asp in human PTEN. In about 2 of your present proteins, by contrast, the corresponding side chain cannot ionize. In the Capitella teleta protein this residue is Gln, and in the Riptortus pedestris protein it is actually Pro. Ten of 2 such cases are correlated with all the insubstitution of an acidic side chain within the signature motif. In the C. teleta protein the motif is WPQ. . .IHSKGERGRS. The Capsaspora owczarzaki and Paramecium tetraurelia proteins are exceptions.Figure 2. Location in PTEN from the PTPC2 superdomain conserved motifs. The PTP domain is at the leading in each and every case, the C2 domain at the bottom. A) Motif , PS(QH)(K R)RYUXYF. B) Motif 2, U2GDU3(RK)UYH. C) Motif three, UFXUQFHTU2. D) Motif four, KX(DE)L(DE)X5(RK). All atoms of every residue in each and every motif are shown spacefilled and colored orange. The D5R structure was utilized for visualization.PTPC2 evolutionAdditional proof supports the claimed existence of a PTPC2 superdomain, which is, the inheritance with the two domains a single PF-2771 web structural unit. Figure 4 shows a schematic of your molecular architecture of exemplars from the present set of proteins. A important example not shown is the human putative membrane protein EAX08222, in which PTPC2 is at theconserved helix in PTP discussed above. The locations in 
PTEN in the four novel motifs identified right here are shown in Figure 2. Each and every tends to make a considerable contribution for the domain interface. Finally, the sequence data also recommend that b strandrich C2 is additional tolerant of turnlength variations than is mixed ab PTP in PTPC2 (see Supporting Details).Charge properties of PTPCTwo additional points relating to electric charge are worth noting. One particular, the pI of PTPC2 is fundamental for all of the animal proteins studied right here, regardless of divergence from human TNS3 (circles, Fig. three). The plant proteins, by contrast, shown as squares, are about 25 identical to human TNS3 in PTPC2 but are acidic (squares). The physiological significance of those differences is unclear. A distinctive feature in the plant proteins can be a formin homology 2 (FH2) domain downstream of PTPC2. Required for the selfassociation of formin proteins, FH2 also influences actin polymerization in Saccharomyces cerevisiae.3 Inside the present animal proteins, by contrast,Figure 3. Calculated isoelectric point versus nominal percentage identity for the present PTPC2 superdomain sequences. The comparisons were produced with respect to human TNS3. A cyan backgroun.