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3Na0 Lichtarge Lab 2006 Pages 1–11 3na0 Evolutionary trace report by report maker September 13, 2010 4.3.1 Alistat 10 4.3.2 CE 10 4.3.3 DSSP 10 4.3.4 HSSP 11 4.3.5 LaTex 11 4.3.6 Muscle 11 4.3.7 Pymol 11 4.4 Note about ET Viewer 11 4.5 Citing this work 11 4.6 About report maker 11 4.7 Attachments 11 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 3na0): Title: Crystal structure of human cyp11a1 in complex with 20,22- dihydroxycholesterol Compound: Mol id: 1; molecule: cholesterol side-chain cleavage enzyme, mitochond chain: a, b; fragment: unp residues 44-514; syn- onym: cytochrome p450 11a1, cypxia1, cytochrome p450(scc chole- sterol desmolase; ec: 1.14.15.6; engineered: yes; mol id: 2; molecule: CONTENTS adrenodoxin, mitochondrial; chain: c, d; fragment: unp residues 88-155; synonym: adrenal ferredoxin, ferredoxin-1, hepatoredoxin; 1 Introduction 1 engineered: yes Organism, scientific name: Homo Sapiens; 2 Chain 3na0A 1 3na0 contains a single unique chain 3na0A (470 residues long) and 2.1 Q8N1A7 overview 1 its homologue 3na0B. Not enough homologous sequences could be 2.2 Multiple sequence alignment for 3na0A 1 found to permit analysis for chain 3na0C. 2.3 Residue ranking in 3na0A 1 2.4 Top ranking residues in 3na0A and their position on the structure 2 2 CHAIN 3NA0A 2.4.1 Clustering of residues at 25% coverage. 2 2.4.2 Overlap with known functional surfaces at 2.1 Q8N1A7 overview 25% coverage. 2 From SwissProt, id Q8N1A7, 100% identical to 3na0A: 2.4.3 Possible novel functional surfaces at 25% Description: Cytochrome P450, subfamily XIA,. coverage. 6 Organism, scientific name: Homo sapiens (Human). Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; 3 Notes on using trace results 9 Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; 3.1 Coverage 9 Catarrhini; Hominidae; Homo. 3.2 Known substitutions 9 Similarity: Belongs to the cytochrome P450 family. 3.3 Surface 9 3.4 Number of contacts 10 3.5 Annotation 10 2.2 Multiple sequence alignment for 3na0A 3.6 Mutation suggestions 10 For the chain 3na0A, the alignment 3na0A.msf (attached) with 118 sequences was used. The alignment was downloaded from the HSSP 4 Appendix 10 database, and fragments shorter than 75% of the query as well as 4.1 File formats 10 duplicate sequences were removed. It can be found in the attachment 4.2 Color schemes used 10 to this report, under the name of 3na0A.msf. Its statistics, from the 4.3 Credits 10 alistat program are the following: 1 Lichtarge lab 2006 2.4 Top ranking residues in 3na0A and their position on the structure In the following we consider residues ranking among top 25% of residues in the protein . Figure 3 shows residues in 3na0A colored by their importance: bright red and yellow indicate more conser- ved/important residues (see Appendix for the coloring scheme). A Pymol script for producing this figure can be found in the attachment. Fig. 1. Residues 45-279 in 3na0A colored by their relative importance. (See Appendix, Fig.11, for the coloring scheme.) Fig. 2. Residues 280-514 in 3na0A colored by their relative importance. (See Appendix, Fig.11, for the coloring scheme.) Fig. 3. Residues in 3na0A, colored by their relative importance. Clockwise: front, back, top and bottom views. Format: MSF Number of sequences: 118 2.4.1 Clustering of residues at 25% coverage. Fig. 4 shows the Total number of residues: 53345 top 25% of all residues, this time colored according to clusters they Smallest: 356 belong to. The clusters in Fig.4 are composed of the residues listed Largest: 470 in Table 1. Average length: 452.1 Alignment length: 470 Table 1. Average identity: 37% cluster size member Most related pair: 99% color residues Most unrelated pair: 17% red 113 85,86,87,88,89,99,114,115 Most distant seq: 32% 118,120,126,129,130,138,139 144,147,151,154,155,159,167 174,177,178,203,205,208,213 Furthermore, 1% of residues show as conserved in this alignment. 215,216,217,218,220,221,222 The alignment consists of 48% eukaryotic ( 47% vertebrata) 233,234,263,266,270,271,273 sequences. (Descriptions of some sequences were not readily availa- 302,305,311,315,318,319,322 ble.) The file containing the sequence descriptions can be found in 323,326,327,328,329,330,331 the attachment, under the name 3na0A.descr. 334,335,337,339,340,342,343 344,346,349,352,355,356,359 2.3 Residue ranking in 3na0A 375,376,377,378,379,382,383 384,385,386,387,389,390,396 The 3na0A sequence is shown in Figs. 1–2, with each residue colored according to its estimated importance. The full listing of residues continued in next column in 3na0A can be found in the file called 3na0A.ranks sorted in the attachment. 2 Table 2. continued res type subst’s cvg noc/ dist antn (%) bb (A˚ ) 466 R R(94) 0.09 16/0 3.37 .(4)F 465 R R(87) 0.12 9/0 3.40 K(7)T .(4) 159 M L(54) 0.13 22/9 3.34 M(35) F(2) I(6)H 378 K R(32) 0.13 15/0 3.27 K(66)W 450 F F(87) 0.14 46/7 3.36 Y(6)T S(1)R .(1)A 155 N N(71) 0.16 26/8 3.64 S(4) A(5) R(1) Fig. 4. Residues in 3na0A, colored according to the cluster they belong to: Q(10) red, followed by blue and yellow are the largest clusters (see Appendix for D(5)G the coloring scheme). Clockwise: front, back, top and bottom views. The 461 Q Q(54) 0.20 18/0 2.97 corresponding Pymol script is attached. S(10) A(9) M(19) Table 1. continued G(1)R cluster size member .(4) color residues 469 E E(88) 0.23 4/0 4.31 401,404,407,409,410,411,413 Q(3) 415,423,429,432,435,437,439 .(5)GV 440,454,455,456,458,460,461 462,464,465,466,468,469,471 blue 2 104,450 Table 2. The top 25% of residues in 3na0A at the interface with 3na0C. (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 Table 1. Clusters of top ranking residues in 3na0A. 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. ) 2.4.2 Overlap with known functional surfaces at 25% coverage. The name of the ligand is composed of the source PDB identifier and the heteroatom name used in that file. Table 3. Interface with 3na0C.Table 2 lists the top 25% of residues at the res type disruptive interface with 3na0C. The following table (Table 3) suggests possible mutations disruptive replacements for these residues (see Section 3.6). 151 R (TD)(SYEVCLAPIG)(FMW)(N) 382 K (Y)(T)(FW)(SVCAG) Table 2. 458 G (KER)(FQMWHD)(NLPI)(Y) res type subst’s cvg noc/ dist antn 456 G (K)(ER)(Q)(MD) A˚ (%) bb ( ) 466 R (TD)(SECG)(VLAPI)(Y) 151 R R(100) 0.01 1/0 4.84 465 R (D)(T)(YVLAPI)(SFECWG) 382 K K(96) 0.03 9/0 2.66 159 M (Y)(T)(R)(S) R(3) 378 K (TY)(SCG)(FVAWD)(E) 458 G G(96) 0.05 13/13 3.12 450 F (K)(E)(Q)(D) .(3) 155 N (Y)(FWH)(T)(R) 456 G G(94)W 0.07 1/1 4.85 site 461 Q (Y)(H)(FW)(T) .(3)S continued in next column continued in next column 3 Table 3. continued Table 4. continued res type disruptive res type subst’s cvg noc/ dist antn mutations (%) bb (A˚ ) 469 E (H)(FW)(Y)(R) 460 R R(94) 0.06 38/17 2.73 site .(4)P Table 3. List of disruptive mutations for the top 25% of residues in 462 C C(94)S 0.06 70/33 2.33 site 3na0A, that are at the interface with 3na0C. .(4) 464 G G(94)R 0.06 35/35 3.53 site .(4) 456 G G(94)W 0.07 10/10 3.46 site .(3)S 385 L L(85) 0.08 5/0 3.60 site M(8) F(2)IQE S 468 A A(94) 0.09 10/2 3.76 .(4)P 331 T T(83) 0.10 9/4 4.08 V(9) A(3)I S(2) 323 M L(74) 0.12 13/7 3.25 site M(19) V(3) I(1)G 334 T P(22) 0.12 5/0 3.37 site T(59)V S(13)G A(1)D 327 G S(19) 0.13 12/12 3.57 site G(66) A(14) Fig. 5. Residues in 3na0A, at the interface with 3na0C, colored by their rela- 322 E D(13) 0.17 3/1 4.47 tive importance. 3na0C is shown in backbone representation (See Appendix E(83)GP for the coloring scheme for the protein chain 3na0A.) K 326 G G(69) 0.18 23/23 3.68 site Figure 5 shows residues in 3na0A colored by their importance, at the A(28).H interface with 3na0C.
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