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1Wmh Lichtarge Lab 2006 Pages 1–9 1wmh Evolutionary trace report by report maker December 24, 2009 4 Notes on using trace results 7 4.1 Coverage 7 4.2 Known substitutions 7 4.3 Surface 7 4.4 Number of contacts 7 4.5 Annotation 8 4.6 Mutation suggestions 8 5 Appendix 8 5.1 File formats 8 5.2 Color schemes used 8 5.3 Credits 8 5.3.1 Alistat 8 5.3.2 CE 8 5.3.3 DSSP 8 5.3.4 HSSP 8 5.3.5 LaTex 9 5.3.6 Muscle 9 5.3.7 Pymol 9 5.4 Note about ET Viewer 9 5.5 Citing this work 9 5.6 About report maker 9 CONTENTS 5.7 Attachments 9 1 Introduction 1 1 INTRODUCTION From the original Protein Data Bank entry (PDB id 1wmh): 2 Chain 1wmhA 1 Title: Crystal structure of a pb1 domain complex of protein kinase c 2.1 Q5R4K9 overview 1 iota and par6 alpha 2.2 Multiple sequence alignment for 1wmhA 1 Compound: Mol id: 1; molecule: protein kinase c, iota type; chain: 2.3 Residue ranking in 1wmhA 1 a; fragment: pb1 domain; synonym: npkc-iota, atypical protein 2.4 Top ranking residues in 1wmhA and their position kinase c-lambda/iota, apkc-lambda/iota; ec: 2.7.1.37; engineered: on the structure 2 yes; mol id: 2; molecule: partitioning defective-6 homolog alpha; 2.4.1 Clustering of residues at 25% coverage. 2 chain: b; fragment: pb1 domain; synonym: par-6 alpha, par-6a, par-6, 2.4.2 Overlap with known functional surfaces at par6c, tax interaction protein 40, tip-40; engineered: yes 25% coverage. 2 Organism, scientific name: Homo Sapiens; 2.4.3 Possible novel functional surfaces at 25% 1wmh contains unique chains 1wmhA (83 residues) and 1wmhB coverage. 3 (82 residues) 3 Chain 1wmhB 4 2 CHAIN 1WMHA 3.1 Q9NPB6 overview 4 3.2 Multiple sequence alignment for 1wmhB 4 2.1 Q5R4K9 overview 3.3 Residue ranking in 1wmhB 4 From SwissProt, id Q5R4K9, 100% identical to 1wmhA: 3.4 Top ranking residues in 1wmhB and their position Description: Protein kinase C, iota type (EC 2.7.1.37) (nPKC-iota). on the structure 5 Organism, scientific name: Pongo pygmaeus (Orangutan). 3.4.1 Clustering of residues at 26% coverage. 5 Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; 3.4.2 Overlap with known functional surfaces at Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; 26% coverage. 5 Catarrhini; Hominidae; Pongo. 3.4.3 Possible novel functional surfaces at 26% Function: Calcium-independent, phospholipid-dependent, serine- coverage. 6 and threonine-specific enzyme. Is not activated by phorbol esters 1 Lichtarge lab 2006 or diaglycerol. May play role in the secretory response to nutrients. Involved in cell polarization processes and the formation of epithelial tight junctions (By similarity). Catalytic activity: ATP + a protein = ADP + a phosphoprotein. Enzyme regulation: Might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion (By similarity). Fig. 1. Residues 16-98 in 1wmhA colored by their relative importance. (See Subunit: Interacts with PARD6A, PARD6B and PARD6G. Part Appendix, Fig.12, for the coloring scheme.) of a quaternary complex containing PARD3, some PARD6 pro- tein (PARD6A, PARD6B or PARD6G) and some GTPase protein (CDC42 or RAC1). Interacts with CENTA1 (By similarity). Pymol script for producing this figure can be found in the attachment. Similarity: Belongs to the Ser/Thr protein kinase family. PKC subfamily. Similarity: Contains 1 phorbol-ester/DAG-type zinc finger. About: This Swiss-Prot entry is copyright. It is produced through a collaboration between the Swiss Institute of Bioinformatics and the EMBL outstation - the European Bioinformatics Institute. There are no restrictions on its use as long as its content is in no way modified and this statement is not removed. 2.2 Multiple sequence alignment for 1wmhA For the chain 1wmhA, the alignment 1wmhA.msf (attached) with 31 sequences was used. The alignment was downloaded from the HSSP database, and fragments shorter than 75% of the query as well as duplicate sequences were removed. It can be found in the attachment to this report, under the name of 1wmhA.msf. Its statistics, from the alistat program are the following: Format: MSF Number of sequences: 31 Total number of residues: 2540 Smallest: 73 Largest: 83 Average length: 81.9 Alignment length: 83 Average identity: 50% Most related pair: 99% Fig. 2. Residues in 1wmhA, colored by their relative importance. Clockwise: Most unrelated pair: 13% front, back, top and bottom views. Most distant seq: 33% Furthermore, 3% of residues show as conserved in this alignment. 2.4.1 Clustering of residues at 25% coverage. Fig. 3 shows the The alignment consists of 41% eukaryotic ( 25% vertebrata, 6% top 25% of all residues, this time colored according to clusters they arthropoda) sequences. (Descriptions of some sequences were not belong to. The clusters in Fig.3 are composed of the residues listed readily available.) The file containing the sequence descriptions can in Table 1. be found in the attachment, under the name 1wmhA.descr. Table 1. 2.3 Residue ranking in 1wmhA cluster size member color residues The 1wmhA sequence is shown in Fig. 1, with each residue colored red 19 20,29,58,60,61,63,65,67,68 according to its estimated importance. The full listing of residues in 69,73,76,77,79,80,82,83,92 1wmhA can be found in the file called 1wmhA.ranks sorted in the 95 attachment. 2.4 Top ranking residues in 1wmhA and their position Table 1. Clusters of top ranking residues in 1wmhA. on the structure In the following we consider residues ranking among top 25% of residues in the protein . Figure 2 shows residues in 1wmhA colored 2.4.2 Overlap with known functional surfaces at 25% coverage. by their importance: bright red and yellow indicate more conser- The name of the ligand is composed of the source PDB identifier ved/important residues (see Appendix for the coloring scheme). A and the heteroatom name used in that file. 2 Table 2. continued res type subst’s cvg noc/ dist (%) bb (A˚ ) Table 2. The top 25% of residues in 1wmhA at the interface with 1wmhB. (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. res type disruptive mutations 63 D (R)(FWH)(KYVCAG)(TQM) 67 D (R)(FWH)(KYVCAG)(TQM) 79 E (FWH)(YVCARG)(T)(SNKLPI) 61 W (K)(E)(Q)(D) 68 P (Y)(T)(HR)(SCG) 76 E (FWH)(R)(YVCAG)(T) 82 R (D)(ELPI)(FTYVMAW)(SCG) 65 E (FWH)(R)(YVCAG)(T) Fig. 3. Residues in 1wmhA, colored according to the cluster they belong to: red, followed by blue and yellow are the largest clusters (see Appendix for 83 L (YR)(H)(T)(KE) the coloring scheme). Clockwise: front, back, top and bottom views. The 69 C (E)(KR)(D)(YH) corresponding Pymol script is attached. Table 3. List of disruptive mutations for the top 25% of residues in 1wmhA, that are at the interface with 1wmhB. Interface with 1wmhB.Table 2 lists the top 25% of residues at the interface with 1wmhB. The following table (Table 3) suggests possible disruptive replacements for these residues (see Section 4.6). Table 2. res type subst’s cvg noc/ dist (%) bb (A˚ ) 63 D D(100) 0.04 22/0 2.73 67 D D(100) 0.04 33/3 2.71 79 E E(100) 0.04 49/0 3.19 61 W W(96) 0.12 9/0 3.82 Y(3) 68 P P(96) 0.12 12/11 3.61 K(3) 76 E E(96) 0.12 38/5 2.80 D(3) 82 R R(96) 0.12 24/0 3.25 T(3) 65 E E(90) 0.18 28/1 2.62 D(9) 83 L L(83) 0.24 15/0 3.57 I(6) C(6) M(3) 69 C C(83) 0.25 29/11 3.27 I(9) Fig. 4. Residues in 1wmhA, at the interface with 1wmhB, colored by V(3) their relative importance. 1wmhB is shown in backbone representation (See R(3) Appendix for the coloring scheme for the protein chain 1wmhA.) continued in next column Figure 4 shows residues in 1wmhA colored by their importance, at the interface with 1wmhB. 3 2.4.3 Possible novel functional surfaces at 25% coverage. One Table 4. continued group of residues is conserved on the 1wmhA surface, away from (or res type substitutions(%) cvg susbtantially larger than) other functional sites and interfaces reco- M(3) gnizable in PDB entry 1wmh. It is shown in Fig. 5. The residues 69 C C(83)I(9)V(3) 0.25 R(3) Table 4. Residues forming surface ”patch” in 1wmhA. Table 5. res type disruptive mutations 63 D (R)(FWH)(KYVCAG)(TQM) 67 D (R)(FWH)(KYVCAG)(TQM) 79 E (FWH)(YVCARG)(T)(SNKLPI) 58 T (R)(K)(H)(FQW) 60 K (Y)(FTW)(SVCAG)(H) 61 W (K)(E)(Q)(D) 68 P (Y)(T)(HR)(SCG) 76 E (FWH)(R)(YVCAG)(T) 77 L (YR)(TH)(SKECG)(FQWD) 82 R (D)(ELPI)(FTYVMAW)(SCG) 95 H (T)(E)(D)(CG) 80 A (KR)(YE)(QH)(D) 92 L (YR)(TH)(SKECG)(FQWD) 65 E (FWH)(R)(YVCAG)(T) 73 S (KR)(FQMWH)(NELPI)(Y) Fig.
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