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2Zw4 Lichtarge Lab 2006 Pages 1–11 2zw4 Evolutionary trace report by report maker April 21, 2010 4.3.3 DSSP 10 4.3.4 HSSP 10 4.3.5 LaTex 10 4.3.6 Muscle 10 4.3.7 Pymol 10 4.4 Note about ET Viewer 10 4.5 Citing this work 10 4.6 About report maker 10 4.7 Attachments 10 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 2zw4): Title: Crystal structure of bleomycin n-acetyltransferase complexed with coenzyme a in the orthorhombic crystal Compound: Mol id: 1; molecule: bleomycin acetyltransferase; CONTENTS chain: a, b, c, d; engineered: yes Organism, scientific name: Streptomyces Verticillus; 1 Introduction 1 2zw4 contains a single unique chain 2zw4A (294 residues long) and its homologues 2zw4D, 2zw4C, and 2zw4B. 2 Chain 2zw4A 1 2.1 Q53796 overview 1 2.2 Multiple sequence alignment for 2zw4A 1 2.3 Residue ranking in 2zw4A 1 2.4 Top ranking residues in 2zw4A and their position on the structure 2 2 CHAIN 2ZW4A 2.4.1 Clustering of residues at 25% coverage. 2 2.4.2 Overlap with known functional surfaces at 2.1 Q53796 overview 25% coverage. 2 From SwissProt, id Q53796, 90% identical to 2zw4A: Description: Bleomycin acetyltransferase. 3 Notes on using trace results 9 Organism, scientific name: Streptomyces verticillus. 3.1 Coverage 9 Taxonomy: Bacteria; Actinobacteria; Actinobacteridae; Actinomy- 3.2 Known substitutions 9 cetales; Streptomycineae; Streptomycetaceae; Streptomyces. 3.3 Surface 9 3.4 Number of contacts 9 3.5 Annotation 9 3.6 Mutation suggestions 9 2.2 Multiple sequence alignment for 2zw4A 4 Appendix 9 For the chain 2zw4A, the alignment 2zw4A.msf (attached) with 27 4.1 File formats 9 sequences was used. The alignment was downloaded from the HSSP 4.2 Color schemes used 9 database, and fragments shorter than 75% of the query as well as 4.3 Credits 9 duplicate sequences were removed. It can be found in the attachment 4.3.1 Alistat 9 to this report, under the name of 2zw4A.msf. Its statistics, from the 4.3.2 CE 10 alistat program are the following: 1 Lichtarge lab 2006 Fig. 1. Residues 8-154 in 2zw4A colored by their relative importance. (See Appendix, Fig.12, for the coloring scheme.) Fig. 2. Residues 155-301 in 2zw4A colored by their relative importance. (See Appendix, Fig.12, for the coloring scheme.) Fig. 3. Residues in 2zw4A, colored by their relative importance. Clockwise: Format: MSF front, back, top and bottom views. Number of sequences: 27 Total number of residues: 4866 Smallest: 119 belong to. The clusters in Fig.4 are composed of the residues listed Largest: 294 Average length: 180.2 Alignment length: 294 Average identity: 26% Most related pair: 99% Most unrelated pair: 0% Most distant seq: 31% Furthermore, <1% of residues show as conserved in this ali- gnment. The alignment consists of 7% prokaryotic sequences. (Descripti- ons of some sequences were not readily available.) The file contai- ning the sequence descriptions can be found in the attachment, under the name 2zw4A.descr. 2.3 Residue ranking in 2zw4A The 2zw4A sequence is shown in Figs. 1–2, with each residue colo- red according to its estimated importance. The full listing of residues in 2zw4A can be found in the file called 2zw4A.ranks sorted in the attachment. 2.4 Top ranking residues in 2zw4A and their position on the structure In the following we consider residues ranking among top 25% of Fig. 4. Residues in 2zw4A, colored according to the cluster they belong to: residues in the protein . Figure 3 shows residues in 2zw4A colored red, followed by blue and yellow are the largest clusters (see Appendix for by their importance: bright red and yellow indicate more conser- the coloring scheme). Clockwise: front, back, top and bottom views. The ved/important residues (see Appendix for the coloring scheme). A corresponding Pymol script is attached. Pymol script for producing this figure can be found in the attachment. in Table 1. 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 2 Table 1. Table 2. continued cluster size member res type subst’s cvg noc/ dist antn color residues (%) bb (A˚ ) red 70 12,13,14,16,17,19,20,27,28 .(7) 31,33,36,37,39,40,42,43,44 97 W W(44) 0.08 34/12 3.15 site 67,69,71,82,85,86,94,95,96 Y(29) 97,99,101,104,105,106,107 C(3) 108,109,110,111,112,113,115 F(11) 116,117,119,120,121,124,125 .(11) 126,128,129,131,132,134,135 40 V V(66) 0.09 12/8 3.31 site 137,139,140,142,143,144,146 I(3) 147,148,149,152,153,167,170 L(3) 171 .(11) blue 2 77,78 T(3) A(7) Table 1. Clusters of top ranking residues in 2zw4A. C(3) 96 T G(59) 0.10 4/2 4.34 T(14) 2.4.2 Overlap with known functional surfaces at 25% coverage. S(3) The name of the ligand is composed of the source PDB identifier N(3) and the heteroatom name used in that file. .(11) Coenzyme a binding site. Table 2 lists the top 25% of residues at A(3) the interface with 2zw4ACOA401 (coenzyme a). The following table L(3) (Table 3) suggests possible disruptive replacements for these residues 110 T T(62) 0.11 13/5 2.41 site (see Section 3.6). V(3) .(11) Table 2. R(7) res type subst’s cvg noc/ dist antn A(7) A˚ (%) bb ( ) H(3) 16 R R(85) 0.01 17/0 3.41 site S(3) E(3) 109 A A(62) 0.12 21/11 2.90 .(11) T(3) 105 G G(88) 0.01 45/45 2.66 V(7) .(11) .(11) 107 G G(88) 0.01 48/48 3.18 site G(7) .(11) M(7) 137 N N(85) 0.02 10/0 2.98 site 108 Y Y(62) 0.14 10/9 3.08 site D(3) L(14) .(11) .(11) 140 S S(77) 0.03 13/2 3.13 F(7) A(11) V(3) .(11) 95 L V(11) 0.16 1/1 4.28 104 W W(70) 0.05 65/8 2.97 site L(51) R(11) .(11) H(3) I(25) Q(3) 99 L F(14) 0.16 23/9 3.10 site .(11) L(59) 139 R A(48) 0.07 36/4 2.53 site Y(3) R(37) C(3) P(3) V(3) .(11) .(11) 143 V V(74) 0.07 8/0 3.74 I(3) T(7) 146 R R(51) 0.16 29/0 2.71 site M(3) K(25) L(7) G(7) continued in next column continued in next column 3 Table 2. continued Table 3. continued res type subst’s cvg noc/ dist antn res type disruptive (%) bb (A˚ ) mutations Q(3) 97 W (K)(E)(Q)(D) .(7) 40 V (R)(K)(YE)(H) A(3) 96 T (R)(K)(H)(FW) 43 W F(14) 0.17 9/4 3.67 site 110 T (K)(R)(Q)(M) W(37) 109 A (R)(K)(Y)(E) Y(25) 108 Y (K)(Q)(ER)(M) H(7) 95 L (YR)(H)(T)(KE) P(3) 99 L (R)(Y)(K)(H) .(11) 146 R (D)(TY)(E)(S) 132 W M(3) 0.22 1/1 4.42 43 W (K)(E)(Q)(T) W(18) 132 W (K)(E)(T)(Q) E(18) 106 H (T)(E)(D)(S) V(18) 44 W (K)(E)(Q)(DR) Y(3) R(7) Table 3. List of disruptive mutations for the top 25% of residues in .(11) 2zw4A, that are at the interface with coenzyme a. F(7) D(7) I(3) 106 H K(11) 0.23 50/48 3.23 site H(29) L(3) R(22) Q(22) .(11) 44 W V(3) 0.24 14/0 3.62 W(40) T(3) Y(11) L(14) I(3) .(11) F(11) Table 2. The top 25% of residues in 2zw4A at the interface with coen- zyme a.(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 num- ber of contacts realized through backbone atoms given in the bracket; dist: distance of closest apporach to the ligand. ) Fig. 5. Residues in 2zw4A, at the interface with coenzyme a, colored by their Table 3. relative importance. The ligand (coenzyme a) is colored green. Atoms further res type disruptive than 30A˚ away from the geometric center of the ligand, as well as on the line mutations of sight to the ligand were removed. (See Appendix for the coloring scheme 16 R (T)(VCAG)(Y)(SLPDI) for the protein chain 2zw4A.) 105 G (KER)(FQMWHD)(NLPI)(Y) 107 G (KER)(FQMWHD)(NLPI)(Y) 137 N (Y)(FWH)(T)(VCARG) Figure 5 shows residues in 2zw4A colored by their importance, at the 140 S (KR)(H)(Q)(FMW) interface with 2zw4ACOA401. 104 W (E)(T)(D)(K) Interface with 2zw4B.Table 4 lists the top 25% of residues at 139 R (TD)(Y)(E)(SCG) the interface with 2zw4B. The following table (Table 5) suggests 143 V (R)(Y)(K)(H) possible disruptive replacements for these residues (see Section 3.6).
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