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2Oc3 Lichtarge Lab 2006 Pages 1–5 2oc3 Evolutionary trace report by report maker September 25, 2008 4.3.3 DSSP 5 4.3.4 HSSP 5 4.3.5 LaTex 5 4.3.6 Muscle 5 4.3.7 Pymol 5 4.4 Note about ET Viewer 5 4.5 Citing this work 5 4.6 About report maker 5 4.7 Attachments 5 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 2oc3): Title: Crystal structure of the catalytic domain of human protein tyrosine phosphatase non-receptor type 18 Compound: Mol id: 1; molecule: tyrosine-protein phosphatase non- receptor type 18; chain: a; synonym: brain-derived phosphatase; ec: CONTENTS 3.1.3.48; engineered: yes Organism, scientific name: 1 Introduction 1 Homo Sapiens; 2oc3 contains a single unique chain 2oc3A (279 residues long). 2 Chain 2oc3A 1 2.1 Q53P42 overview 1 2.2 Multiple sequence alignment for 2oc3A 1 2.3 Residue ranking in 2oc3A 1 2.4 Top ranking residues in 2oc3A and their position on the structure 1 2 CHAIN 2OC3A 2.4.1 Clustering of residues at 25% coverage. 2 2.1 Q53P42 overview 2.4.2 Possible novel functional surfaces at 25% From SwissProt, id Q53P42, 96% identical to 2oc3A: coverage. 2 Description: Hypothetical protein PTPN18. Organism, scientific name: Homo sapiens (Human). 3 Notes on using trace results 3 Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; 3.1 Coverage 3 Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; 3.2 Known substitutions 3 Catarrhini; Hominidae; Homo. 3.3 Surface 4 3.4 Number of contacts 4 3.5 Annotation 4 3.6 Mutation suggestions 4 2.2 Multiple sequence alignment for 2oc3A 4 Appendix 4 For the chain 2oc3A, the alignment 2oc3A.msf (attached) with 49 4.1 File formats 4 sequences was used. The alignment was assembled through combi- 4.2 Color schemes used 4 nation of BLAST searching on the UniProt database and alignment 4.3 Credits 4 using Muscle program. It can be found in the attachment to this 4.3.1 Alistat 4 report, under the name of 2oc3A.msf. Its statistics, from the alistat 4.3.2 CE 5 program are the following: 1 Lichtarge lab 2006 Fig. 1. Residues 6-153 in 2oc3A colored by their relative importance. (See Appendix, Fig.6, for the coloring scheme.) Fig. 2. Residues 154-293 in 2oc3A colored by their relative importance. (See Appendix, Fig.6, for the coloring scheme.) Fig. 3. Residues in 2oc3A, colored by their relative importance. Clockwise: Format: MSF front, back, top and bottom views. Number of sequences: 49 Total number of residues: 13301 Smallest: 254 Largest: 279 Average length: 271.4 Alignment length: 279 Average identity: 38% Most related pair: 99% Most unrelated pair: 22% Most distant seq: 42% Furthermore, 3% of residues show as conserved in this alignment. The alignment consists of 97% eukaryotic ( 87% vertebrata, 2% arthropoda) sequences. (Descriptions of some sequences were not readily available.) The file containing the sequence descriptions can be found in the attachment, under the name 2oc3A.descr. 2.3 Residue ranking in 2oc3A The 2oc3A sequence is shown in Figs. 1–2, with each residue colored according to its estimated importance. The full listing of residues in 2oc3A can be found in the file called 2oc3A.ranks sorted in the attachment. 2.4 Top ranking residues in 2oc3A and their position on Fig. 4. Residues in 2oc3A, colored according to the cluster they belong to: the structure red, followed by blue and yellow are the largest clusters (see Appendix for the coloring scheme). Clockwise: front, back, top and bottom views. The In the following we consider residues ranking among top 25% of corresponding Pymol script is attached. residues in the protein . Figure 3 shows residues in 2oc3A colored by their importance: bright red and yellow indicate more conser- ved/important residues (see Appendix for the coloring scheme). A in Table 1. Pymol script for producing this figure can be found in the attachment. 2.4.1 Clustering of residues at 25% coverage. Fig. 4 shows the top 25% of all residues, this time colored according to clusters they belong to. The clusters in Fig.4 are composed of the residues listed 2 Table 1. Table 2. continued cluster size member res type substitutions(%) cvg color residues 234 G G(91)K(2)V(6) 0.08 red 68 56,59,60,61,67,69,72,73,85 268 R R(91)N(8) 0.08 86,87,88,89,90,91,92,101,102 195 W W(97).(2) 0.09 103,104,105,106,107,108,111 201 P P(97).(2) 0.09 114,115,116,118,120,121,127 72 R R(93)L(6) 0.10 128,129,130,131,135,141,144 230 S S(89)L(4)E(6) 0.10 145,146,174,176,185,189,195 108 L L(91)M(6)F(2) 0.11 196,201,224,227,228,229,230 235 R R(91)K(2)S(4) 0.12 232,234,235,236,237,264,268 T(2) 270,271,275,277,280,281,283 224 P P(93)S(4)R(2) 0.14 285 69 D E(18)D(75)P(6) 0.16 blue 2 208,211 87 I V(4)I(93)T(2) 0.16 85 D D(83)K(2)N(4) 0.18 Table 1. Clusters of top ranking residues in 2oc3A. S(6)G(4) 135 E E(87)D(2)P(4) 0.18 S(4)N(2) 2.4.2 Possible novel functional surfaces at 25% coverage. One 280 Q Q(91)A(2)S(2) 0.19 group of residues is conserved on the 2oc3A surface, away from (or E(2)H(2) susbtantially larger than) other functional sites and interfaces reco- 283 F F(77)G(2)L(18) 0.19 gnizable in PDB entry 2oc3. It is shown in Fig. 5. The right panel I(2) shows (in blue) the rest of the larger cluster this surface belongs to. 196 P P(91)A(2)Y(4) 0.21 .(2) 101 Y Y(81)L(2)I(2) 0.22 F(14) 128 L V(81)L(6)A(6) 0.23 I(6) 270 Q Q(77)D(6)A(2) 0.23 Y(2)H(2)N(4) M(6) 208 L I(18)L(73)T(2) 0.24 F(6) 211 V I(53)L(18)V(16) 0.24 R(12) 277 T T(83)L(4)I(2) 0.24 Fig. 5. A possible active surface on the chain 2oc3A. The larger cluster it D(6)S(4) belongs to is shown in blue. 91 F F(61)Y(26)L(4) 0.25 P(8) 227 V V(73)A(2)I(20) 0.25 The residues belonging to this surface ”patch” are listed in Table T(4) 2, while Table 3 suggests possible disruptive replacements for these 285 Y Y(61)H(24)K(2) 0.25 residues (see Section 3.6). F(4)L(8) Table 2. res type substitutions(%) cvg Table 2. Residues forming surface ”patch” in 2oc3A. 59 K K(100) 0.04 61 R R(100) 0.04 105 Q Q(100) 0.04 Table 3. 114 D D(100) 0.04 res type disruptive 115 F F(97)Y(2) 0.05 mutations 229 C C(93)D(6) 0.05 59 K (Y)(FTW)(SVCAG)(HD) 56 N N(93)H(6) 0.06 61 R (TD)(SYEVCLAPIG)(FMW)(N) 60 N N(93)D(6) 0.06 105 Q (Y)(FTWH)(SVCAG)(D) 107 P P(87)C(12) 0.07 114 D (R)(FWH)(KYVCAG)(TQM) 111 T T(97)S(2) 0.07 115 F (K)(E)(Q)(D) 229 C (R)(K)(FWH)(EQM) continued in next column continued in next column 3 Table 3. continued V. The percentage of times the substitution appears in the alignment res type disruptive is given in the immediately following bracket. No percentage is given mutations in the cases when it is smaller than 1%. This is meant to be a rough 56 N (TY)(E)(SFVCAWG)(MHDR) guide - due to rounding errors these percentages often do not add up 60 N (Y)(FWH)(TR)(VCAG) to 100%. 107 P (R)(Y)(H)(KE) 111 T (KR)(FQMWH)(NELPI)(D) 3.3 Surface 234 G (E)(R)(FYWH)(KD) To detect candidates for novel functional interfaces, first we look for 268 R (T)(YD)(SEVCAG)(FLWPI) residues that are solvent accessible (according to DSSP program) by 2 195 W (KE)(TQD)(SNCG)(R) at least 10A˚ , which is roughly the area needed for one water mole- 201 P (YR)(TH)(SCG)(KE) cule to come in the contact with the residue. Furthermore, we require 72 R (T)(YD)(SECG)(VA) that these residues form a “cluster” of residues which have neighbor 230 S (R)(KH)(FW)(Y) within 5A˚ from any of their heavy atoms. 108 L (YR)(T)(H)(KECG) Note, however, that, if our picture of protein evolution is correct, 235 R (D)(Y)(FTELWPI)(VA) the neighboring residues which are not surface accessible might be 224 P (Y)(R)(H)(T) equally important in maintaining the interaction specificity - they 69 D (R)(H)(FW)(Y) should not be automatically dropped from consideration when choo- 87 I (R)(Y)(H)(K) sing the set for mutagenesis. (Especially if they form a cluster with 85 D (R)(FW)(H)(Y) the surface residues.) 135 E (H)(FW)(R)(Y) 3.4 Number of contacts 280 Q (Y)(FWH)(T)(CG) 283 F (KE)(R)(TQD)(S) Another column worth noting is denoted “noc/bb”; it tells the num- 196 P (R)(Y)(KH)(TE) ber of contacts heavy atoms of the residue in question make across 101 Y (K)(QR)(E)(M) the interface, as well as how many of them are realized through the 128 L (YR)(H)(TKE)(SQCDG) backbone atoms (if all or most contacts are through the backbone, 270 Q (Y)(T)(H)(FW) mutation presumably won't have strong impact).
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