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2Fbm Lichtarge Lab 2006 Pages 1–8 2fbm Evolutionary trace report by report maker September 19, 2008 4.3.1 Alistat 7 4.3.2 CE 7 4.3.3 DSSP 7 4.3.4 HSSP 7 4.3.5 LaTex 7 4.3.6 Muscle 7 4.3.7 Pymol 7 4.4 Note about ET Viewer 7 4.5 Citing this work 7 4.6 About report maker 8 4.7 Attachments 8 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 2fbm): Title: Acetyltransferase domain of cdy1 Compound: Mol id: 1; molecule: y chromosome chromodomain protein 1, telomeric isoform b; chain: a, b, c; engineered: yes Organism, scientific name: Homo Sapiens; 2fbm contains a single unique chain 2fbmA (251 residues long) and its homologues 2fbmC and 2fbmB. CONTENTS 2 CHAIN 2FBMA 1 Introduction 1 2.1 Q9Y6F8 overview 2 Chain 2fbmA 1 From SwissProt, id Q9Y6F8, 100% identical to 2fbmA: Description: 2.1 Q9Y6F8 overview 1 Testis-specific chromodomain protein Y 1. Organism, scientific name: 2.2 Multiple sequence alignment for 2fbmA 1 Homo sapiens (Human). Taxonomy: 2.3 Residue ranking in 2fbmA 1 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; 2.4 Top ranking residues in 2fbmA and their position on Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; the structure 2 Catarrhini; Hominidae; Homo. Subcellular location: 2.4.1 Clustering of residues at 25% coverage. 2 Nuclear (By similarity). Alternative products: 2.4.2 Overlap with known functional surfaces at 25% coverage. 2 Event=Alternative splicing; Named isoforms=2; Name=1; 2.4.3 Possible novel functional surfaces at 25% IsoId=Q9Y6F8-1; Sequence=Displayed; Name=2; IsoId=Q9Y6F8- coverage. 4 2; Sequence=VSP 001079; Tissue specificity: Testis specific. 3 Notes on using trace results 6 Similarity: Contains 1 chromo domain. 3.1 Coverage 6 About: This Swiss-Prot entry is copyright. It is produced through a 3.2 Known substitutions 6 collaboration between the Swiss Institute of Bioinformatics and the 3.3 Surface 6 EMBL outstation - the European Bioinformatics Institute. There are 3.4 Number of contacts 6 no restrictions on its use as long as its content is in no way modified 3.5 Annotation 6 and this statement is not removed. 3.6 Mutation suggestions 6 2.2 Multiple sequence alignment for 2fbmA 4 Appendix 6 For the chain 2fbmA, the alignment 2fbmA.msf (attached) with 91 4.1 File formats 6 sequences was used. The alignment was assembled through combi- 4.2 Color schemes used 7 nation of BLAST searching on the UniProt database and alignment 4.3 Credits 7 using Muscle program. It can be found in the attachment to this 1 Lichtarge lab 2006 Pymol script for producing this figure can be found in the attachment. Fig. 1. Residues 282-406 in 2fbmA colored by their relative importance. (See Appendix, Fig.8, for the coloring scheme.) Fig. 2. Residues 407-532 in 2fbmA colored by their relative importance. (See Appendix, Fig.8, for the coloring scheme.) report, under the name of 2fbmA.msf. Its statistics, from the alistat program are the following: Fig. 3. Residues in 2fbmA, colored by their relative importance. Clockwise: Format: MSF front, back, top and bottom views. Number of sequences: 91 Total number of residues: 22176 Smallest: 212 2.4.1 Clustering of residues at 25% coverage. Fig. 4 shows the Largest: 251 top 25% of all residues, this time colored according to clusters they Average length: 243.7 belong to. The clusters in Fig.4 are composed of the residues listed Alignment length: 251 in Table 1. Average identity: 30% Most related pair: 99% Table 1. Most unrelated pair: 16% cluster size member Most distant seq: 30% color residues red 62 297,299,300,302,303,307,308 309,327,333,335,336,341,343 Furthermore, <1% of residues show as conserved in this ali- 344,345,346,381,382,385,386 gnment. 387,388,389,391,392,393,394 The alignment consists of 36% eukaryotic ( 26% vertebrata, 1% 395,397,399,402,403,405,407 arthropoda, 4% fungi, 1% plantae), 50% prokaryotic, and 12% 411,413,416,417,421,424,425 archaean sequences. (Descriptions of some sequences were not rea- 427,428,429,432,437,441,453 dily available.) The file containing the sequence descriptions can be 455,456,460,461,462,465,475 found in the attachment, under the name 2fbmA.descr. 479,494,505,512,528,532 2.3 Residue ranking in 2fbmA Table 1. Clusters of top ranking residues in 2fbmA. The 2fbmA sequence is shown in Figs. 1–2, with each residue colored according to its estimated importance. The full listing of residues in 2fbmA can be found in the file called 2fbmA.ranks sorted in the 2.4.2 Overlap with known functional surfaces at 25% coverage. attachment. The name of the ligand is composed of the source PDB identifier 2.4 Top ranking residues in 2fbmA and their position on and the heteroatom name used in that file. Interface with 2fbmC. the structure Table 2 lists the top 25% of residues at the interface with 2fbmC. The following table (Table 3) suggests possible In the following we consider residues ranking among top 25% of disruptive replacements for these residues (see Section 3.6). residues in the protein . Figure 3 shows residues in 2fbmA colored by their importance: bright red and yellow indicate more conser- ved/important residues (see Appendix for the coloring scheme). A 2 Table 2. continued res type subst’s cvg noc/ dist (%) bb (A˚ ) 405 V I(20) 0.19 5/3 4.25 V(43) R(30) A(3) L(1) 462 V V(74) 0.23 2/2 4.00 A(14) L(3) I(5) C(2) Table 2. The top 25% of residues in 2fbmA at the interface with 2fbmC. (Field names: res: residue number in the PDB entry; type: amino acid type; substs: substitutions seen in the alignment; with the percentage of each type in the bracket; noc/bb: number of contacts with the ligand, with the number of contacts realized through backbone atoms given in the bracket; dist: distance of closest apporach to the ligand. ) Table 3. Fig. 4. Residues in 2fbmA, colored according to the cluster they belong to: res type disruptive red, followed by blue and yellow are the largest clusters (see Appendix for the coloring scheme). Clockwise: front, back, top and bottom views. The mutations corresponding Pymol script is attached. 403 D (R)(K)(FW)(H) 382 P (Y)(R)(H)(T) 460 G (E)(D)(FW)(KYR) Table 2. 461 L (R)(Y)(T)(H) res type subst’s cvg noc/ dist 402 C (K)(ER)(Q)(D) (%) bb (A˚ ) 405 V (Y)(E)(R)(K) 403 D D(97) 0.00 39/28 2.83 462 V (R)(Y)(KE)(H) H(1) T(1) Table 3. List of disruptive mutations for the top 25% of residues in 382 P P(93) 0.03 2/0 4.27 2fbmA, that are at the interface with 2fbmC. I(3) V(1) Figure 5 shows residues in 2fbmA colored by their importance, at the L(1) interface with 2fbmC. M(1) Interface with 2fbmB.Table 4 lists the top 25% of residues at the 460 G G(95) 0.04 13/13 4.03 interface with 2fbmB. The following table (Table 5) suggests possible N(1) disruptive replacements for these residues (see Section 3.6). Q(1) R(1) Table 4. H(1) res type subst’s cvg noc/ dist 461 L L(83) 0.11 1/1 4.78 (%) bb (A˚ ) F(3) 424 P P(80) 0.05 13/3 3.75 I(9) A(14) M(1) N(2) V(2) L(2) 402 C C(71) 0.13 9/9 2.85 S(1) S(4) 437 G G(87) 0.10 8/8 3.96 G(7) S(7) F(7) N(2) A(8) V(1) continued in next column P(1) 512 E E(81) 0.10 6/3 4.19 continued in next column 3 Table 4. continued res type subst’s cvg noc/ dist (%) bb (A˚ ) H(2) C(1) F(2) I(1) Table 4. The top 25% of residues in 2fbmA at the interface with 2fbmB. (Field names: res: residue number in the PDB entry; type: amino acid type; substs: substitutions seen in the alignment; with the percentage of each type in the bracket; noc/bb: number of contacts with the ligand, with the number of contacts realized through backbone atoms given in the bracket; dist: distance of closest apporach to the ligand. ) Table 5. res type disruptive mutations 424 P (YR)(H)(T)(KE) 437 G (R)(KE)(H)(FYW) 512 E (H)(Y)(FW)(R) 417 Y (K)(Q)(E)(R) Fig. 5. Residues in 2fbmA, at the interface with 2fbmC, colored by their rela- tive importance. 2fbmC is shown in backbone representation (See Appendix 421 G (E)(K)(R)(D) for the coloring scheme for the protein chain 2fbmA.) 429 S (KR)(Q)(E)(H) Table 5. List of disruptive mutations for the top 25% of residues in Table 4. continued 2fbmA, that are at the interface with 2fbmB. res type subst’s cvg noc/ dist (%) bb (A˚ ) A(3) M(5) .(3) P(1) G(1) L(1) V(1) S(1) R(1) 417 Y E(42) 0.14 1/1 4.73 F(37) Y(9) W(2) H(3) L(1) C(1) N(1) A(1) 421 G G(87) 0.14 7/7 3.77 A(6) R(3) H(1) S(1) 429 S S(40) 0.20 28/13 3.69 Fig.
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