Mon site SPIP

Auxiliary Activities family classification

2012-11-13T15:29:14Z

Introduction

Auxiliary Activities (AA) cover redox enzymes that act in conjunction with CAZymes.

Since its inception, the carbohydrate-active enzymes database (CAZy ; www.cazy.org) has described the families of enzymes that cleave or build complex carbohydrates, namely the glycoside hydrolases (GH), the polysaccharide lyases (PL), the carbohydrate esterases (CE), the glycosyltransferases (GT) and their appended non-catalytic carbohydrate-binding modules (CBM). The recent discovery that members of families CBM33 and family GH61 are in fact lytic polysaccharide mono-oxygenases (LPMO), demanded a reclassification of these families into a suitable category. Because lignin is invariably found together with polysaccharides in the plant cell wall and because lignin fragments are likely to act in concert with (LPMO)s, we have decided to join the families of lignin degradation enzymes to the LPMO families and launch a new CAZy class that we name "auxiliary activities" in order to accommodate a range of enzyme mechanisms and substrates [1]<pubmed>.

The AA class presently groups 9 families of ligninolytic enzymes and 7 families of lytic polysaccharide mono-oxygenases. Lignin breakdown enzymes may not act on carbohydrates, but because lignin is invariably and intimately associated with carbohydrates in the plant cell wall, the lignolytic enzymes do cooperate with classical polysaccharide depolymerases. This section of the CAZy database presents a classification of these enzymes in families and subfamilies based on amino acid sequence similarities, intended to reflect structural features and to facilitate genome annotation.

Tables for Direct Access

– AA Family Number

Non-Classified Sequences

– AA Classification Statistics

Modules in present families	133312
Non-Classified modules	1607

[1] Levasseur A, Drula E, Lombard V, Coutinho PM, Henrissat B. Expansion of the enzymatic repertoire of the CAZy database to integrate auxiliary redox enzymes. Biotechnology for Biofuels, 6:41 [PMID : 23514094]

Genomes

2009-07-03T13:33:22Z

Introduction

Protein sequences originating from complete genomes and that can be assigned to CAZy families are listed in the links below. The only genomes that are consistently surveyed in the CAZy database are those released by the NCBI as regular entries in the daily releases of GenBank. In a very limited number of cases, we have included data from RefSeq genomes.

The collection of carbohydrate-active enzymes encoded by the genome of an organism ("CAZome") provides an insight into the nature and extent of the metabolism of complex carbohydrates of the species. The CAZomes of free living organisms typically correspond to 1-5% of the predicted coding sequences. Extremely reduced CAZomes are characteristic of species with a strict intracellular parasitic lifestyle. Because of the massive chemical, structural and functional variability of carbohydrates, CAZome analyses and comparisons highlight significant differences between species.

Although often useful, the simple assignment of a protein sequence to a CAZy family does not constitute a refined functional prediction for genomic annotation. For the later task, we are developping a CAZy-based annotation methodology, which takes into account protein modularity, family and subfamily assignment, relatedness to experimentally characterized enzymes and expertise in the varying substrate specificity of carbohydrate-active enzymes. This methodology, which results in coherent, expert and comparable sets of annotations, is applied to novel genomes and metagenomes on a collaborative basis.

NEW : In 2021, we decided to no longer systematically analyze genomes for which at least 60 strains have already been analyzed in CAZy (Organism blacklisted).
Similarly, genomes released as complete but originating from metagenomics data assembly are not systematically analyzed, nor are those from the myriads of clinical isolates of strains already present in CAZy. This allows to focus our curation efforts on the novel explored space.

Tables for Direct Genome Access by Kingdom

Bacteria	37472
Eukaryota	2142
Archaea	595
Viruses	507

Carbohydrate Esterase family classification

2009-07-03T13:28:16Z

Introduction

Carbohydrate esterases catalyze the de-O or de-N-acylation of substituted saccharides. Since an ester = acid + alcohol, we consider two classes of substrates for carbohydrate esterases : those in which the sugar plays the role of the "acid", such as pectin methyl esters and those in which the sugar behaves as the alcohol, such as in acetylated xylan. A number of possible reaction mechanisms may be involved : the most common is a Ser-His-Asp catalytic triad catalyzed deacetylation analogous to the action of classical lipase and serine proteases but other mechanisms such as a Zn2+ catalyzed deacetylation prevails in some families.

The CAZy database provides an updated list of the Carbohydrate Esterase families.

Tables for Direct Access

– CE Family Number

Non-Classified Sequences

– CE Classification Statistics

Modules in present families	227157
Non-Classified modules	8796

Carbohydrate-Binding Module family classification

2009-07-03T12:13:51Z

Introduction

A carbohydrate-binding module (CBM) is defined as a contiguous amino acid sequence within a carbohydrate-active enzyme with a discreet fold having carbohydrate-binding activity . A few exceptions are CBMs in cellulosomal scaffoldin proteins and rare instances of independent putative CBMs. The requirement of CBMs existing as modules within larger enzymes sets this class of carbohydrate-binding protein apart from other non-catalytic sugar binding proteins such as lectins and sugar transport proteins.

CBMs were previously classified as cellulose-binding domains (CBDs) based on the initial discovery of several modules that bound cellulose [1] [2]. However, additional modules in carbohydrate-active enzymes are continually being found that bind carbohydrates other than cellulose yet otherwise meet the CBM criteria, hence the need to reclassify these polypeptides using more inclusive terminology.

Family classification

Previous classification of cellulose-binding domains were based on amino acid similarity [3]. Groupings of CBDs were called "Types" and numbered with roman numerals (e.g. Type I or Type II CBDs). In keeping with the glycoside hydrolase classification, these groupings are now called families and numbered with Arabic numerals. Families 1 to 13 are the same as Types I to XIII [3]. For a detailed review on the structure and binding modes of CBMs see [4].

The family classification of CBMs is expected to :

1. aid in the identification of CBMs

2. in some cases, predict binding specificity

3. aid in identifying functional residues

4. reveal evolutionary relationships

5. be predictive of polypeptide folds

The CAZy database provides an updated list of the CBM-containing proteins, arranged by CBM family. When a protein contains CBMs from different families, it appears in each appropriate family. Because the fold of proteins is better conserved than their sequences, some of the CBM families can be grouped into superfamilies or clans.

Tables for Direct Access

– CBM Family Number

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111

Non-Classified Sequences

– CBM Classification Statistics

Modules in present families	662663
Non-Classified modules	18367

[1] Tomme, P., Van Tilbeurgh, H., Pettersson, G., Van Damme, J., Vandekerckhove, J., Knowles, J., Teeri, T. & Claeyssens, M. (1988) Studies of the cellulolytic system of Trichoderma reesei QM 9414. Analysis of domain function in two cellobiohydrolases by limited proteolysis. Eur. J. Biochem. 170, 575-581 [PMID : 3338453].

[2] Gilkes, N.R., Warren, R.A., Miller, R.C.J. & Kilburn, D.G. (1988) Precise excision of the cellulose binding domains from two Cellulomonas fimi cellulases by a homologous protease and the effect on catalysis. J. Biol. Chem. 263, 10401-10407 [PMID : 3134347].

[3] Tomme, P., Warren, R.A., Miller, R.C., Jr., Kilburn, D.G. & Gilkes, N.R. (1995) in Enzymatic Degradation of Insoluble Polysaccharides (Saddler, J.N. & Penner, M., eds.), Cellulose-binding domains : classification and properties. pp. 142-163, American Chemical Society, Washington.

[4] Boraston, A.B., Bolam, D.N., Gilbert, H.J. & G.J. Davies (2004). Carbohydrate-binding modules : fine tuning polysaccharide recognition. Biochem. J. 382, 769-81 [PMID : 15214846].

Polysaccharide Lyase family classification

2009-07-03T12:07:05Z

Introduction

Polysaccharide Lyases (EC 4.2.2.-) are a group of enzymes that cleave uronic acid-containing polysaccharide chains via a β-elimination mechanism to generate an unsaturated hexenuronic acid residue and a new reducing end. This section of the CAZy database presents a classification of these enzymes in families and subfamilies based on amino acid sequence similarities, intended to reflect their structural features [1].

These enzymes show a large variety of fold types (or classes) [1] [2], suggesting that PLs have been invented more than once during evolution from totally different scaffolds.

Just as for the glycoside hydrolases and the glycosyltransferases, the sequence-based families of polysaccharide lyases are frequently polyspecific (i.e. contain enzymes acting on different substrates or that generate different products). Grouping into mostly monospecific subfamilies described in [1] provides an effort to palliate this polyspecificity. Subfamily information is provided throughout the ensemble of the polysaccharide lyase families described so far.

Catalytic Mechanism

For the purpose of this family classification, the scope of the term PL is restricted to those enzymes which operate according to the general syn- and anti-elimination mechanisms described in [1], to produce a terminal hexenuronic acid moiety by β-elimination. This constitutes a clear distinction from the broader IUBMB classification of carbon-oxygen lyases acting on polysaccharides under EC 4.2.2.-, where other enzyme mechanisms have been described. Several of the lyases non-included in this classification present mechanistic commonality with glycoside hydrolases and have therefore been included among these families.

Tables for Direct Access

– PL Family Number

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44

Non-Classified Sequences

– PL SubFamily Number

PL1	1 2 3 4 5 6 7 8 9 10 11 12 13

PL2	1 2

PL3	1 2 3 4 5

PL4	1 2 3 4 5

PL6	1 2

PL7	1 2 3 4 5

PL8	1 2 3 4

PL9	1 2 3 4

PL10	1 2 3

PL11	1 2

PL12	1 2 3

PL14	1 2 3 4 5

PL15	1 2

PL17	1 2 3 4 5 6

PL22	1 2

– PL Classification Statistics

Modules in present families	88663
Non-Classified modules	3693

[1] Lombard V, Bernard T, Rancurel C, Brumer H, Coutinho PM, Henrissat B (2010) A hierarchical classification of polysaccharide lyases for glycogenomics. Biochem. J. 432:437-444 [PMID : 20925655].

[2] Garron ML, Cygler M (2010) Structural and mechanistic classification of uronic acid-containing polysaccharide lyases Glycobiology, 20:1547-73 [PMID : 20805221].

GlycosylTransferase family classification

2009-07-03T12:00:52Z

Introduction

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases (GTs) (EC 2.4.x.y), the enzymes that catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. Glycosyltransferases can be classified as either retaining or inverting enzymes according to the stereochemistry of the substrates and reaction products [1]. The recommendations of the International Union of Biochemistry and Molecular Biology (IUBMB) do not indicate the intrinsic structural features of the enzymes, nor do they adequately accommodate enzymes which act on several distinct substrates.

The CAZy database proposes the continuously updated classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugars and sugar phosphates (EC 2.4.1.x) and related proteins into distinct sequence-based families as first described by Campbell et al. [2] and then by Coutinho et al. [3]. The same three-dimensional fold is expected to occur within each of the families. Just as for the glycoside hydrolases, several of the families defined on the basis of sequence similarities turn out to have similar three-dimensional structures. Polyspecificity (enzymes with different donor and/or acceptor found in the same family) is common among glycosyltransferase families, making precise functional predictions often unreliable or inaccurate.

Catalytic Mechanism

By analogy with glycosidases, two main stereochemical outcomes exist for glycosyltransferases : inversion of the anomeric configuration (for instance UDP-glucose -> β-glucoside) or retention of the anomeric configuration (for instance UDP-glucose -> α-glucoside).

Inverting glycosyltransferases most likely follow a single displacement mechanism where the acceptor performs a nucleophilic attack at carbon C-1 of the sugar donor somewhat anologous to the mechanism of inverting glycosidases. On the other hand, retaining glycosyltransferases do not appear to operate via a two-step mechanism involving the formation of a glycosyl-enzyme intermediate analogous to glycosidases. Instead, an internal return SNi-like mechanism has been proposed, in which leaving group departure and nucleophilic attack occur in a concerted but asynchronous manner on the same face of the glycoside [4].

Tables for Direct Access

– GT Family Number

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140

Non-Classified Sequences

– GT Classification Statistics

Modules in present families	1827816
Non-Classified modules	91734

[1] Sinnott, M.L. (1990) Catalytic mechanisms of enzymatic glycosyl transfer. Chem. Rev. 90, 1171-1202.

[2] Campbell JA, Davies GJ, Bulone V, Henrissat B (1997) A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem. J. 326:929-939 [PMID : 9334165].

[3] Coutinho PM, Deleury E, Davies GJ, Henrissat B (2003) An evolving hierarchical family classification for glycosyltransferases. J. Mol. Biol. 328:307-317 [PMID : 12691742].

[4] Lairson LL, Henrissat B, Davies GJ, Withers SG (2008) Glycosyltransferases : structures, functions, and mechanisms. Annu Rev Biochem. 77:521-555[PMID : 18518825].

Glycoside Hydrolase family classification

2009-07-02T12:00:11Z

Introduction

Glycoside hydrolases (EC 3.2.1.-) are a widespread group of enzymes which hydrolyse the glycosidic bond between two or more carbohydrates or between a carbohydrate and a non-carbohydrate moiety. The IUBMB Enzyme nomenclature of glycoside hydrolases is based on their substrate specificity and occasionally on their molecular mechanism ; such a classification does not reflect (and was not intended to) the structural features of these enzymes. A classification of glycoside hydrolases in families based on amino acid sequence similarities has been proposed a few years ago. Because there is a direct relationship between sequence and folding similarities, such a classification :

(i) reflects the structural features of these enzymes better than their sole substrate specificity,

(ii) helps to reveal the evolutionary relationships between these enzymes,

(iii) provides a convenient tool to derive mechanistic information [1] [2]

(iv) illustrates the difficulty of deriving relationships between family membership and substrate specificity

The Carbohydrate-Active Enzymes database (CAZy) provides a continuously updated list of the glycoside hydrolase families. Because the fold of proteins is better conserved than their sequences, some of the families can be grouped in 'clans' :
(i) when new sequences are found to be related to more than one family,
(ii) when the sensitivity of sequence comparison methods is increased or
(iii) when structural determinations demonstrate the resemblance between members of different families [3]

The established 'clans' are given in form of a table below.

Catalytic Mechanism

In most cases, the hydrolysis of the glycosidic bond is catalyzed by two amino acid residues of the enzyme : a general acid (proton donor) and a nucleophile/base [4]. Depending on the spatial position of these catalytic residues, hydrolysis occurs via overall retention or overall inversion of the anomeric configuration. For each family listed in the CAZy database, we indicate (when it is known) the stereochemical outcome of the reaction catalyzed as well as the type of amino-acid residues acting as a nucleophile/base and as a proton donor. In some cases, the catalytic nucleophile is not borne by the enzyme, and is replaced by the acetamido group at C-2 of the substrate [5]. A completely unrelated mechanism has been demonstrated recently for two families of glycosidases utilizing NAD+ as a cofactor [6] [7].

For a detailed description of the catalytic mechanism (and variations thereof) of glycoside hydrolases, please visit CAZypedia.

Tables for Direct Access

– GH Family Number

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140	141	142	143	144	145	146	147	148	149	150	151	152	153	154	155	156	157	158	159	160
161	162	163	164	165	166	167	168	169	170	171	172	173	174	175	176	177	178	179	181	182	183	184	185	186	187	188	189	190	191	192	193	194	195

Non-Classified Sequences

– GH SubFamily Number

GH2	1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

GH5	1 2 4 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57

GH13	1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49

GH16	1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

GH19	1 2

GH30	1 2 3 4 5 6 7 8 9 10 11 12

GH31	1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

GH43	1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

GH45	1 2 3 4

GH51	1 2 3 4 5 6 7 8 9 10 11 12 13 14

GH55	1 2 3

GH57	1 2 3 4 5 6 7 8 9 10

GH68	1 2

GH123	1 2 3 4 5 6

GH130	1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

– GH Classification Statistics

Modules in present families	2178303
Non-Classified modules	123489

– GH Clans of Related Families

GH-A	(β/α)₈	1 2 5 10 17 26 30 35 39 42 50 51 53 59 72 79 86 113 128 140 147 148 157 158 164 167 169 173

GH-B	β-jelly roll	7 16

GH-C	β-jelly roll	11 12

GH-D	(β/α)₈	27 31 36

GH-E	6-fold β-propeller	33 34 83 93

GH-F	5-fold β-propeller	43 62 117

GH-G	(α/α)₆	37 63 100

GH-H	(β/α)₈	13 70 77

GH-I	α+β	24 80

GH-J	5-fold β-propeller	32 68

GH-K	(β/α)₈	18 20 85

GH-L	(α/α)₆	15 65 125 178

GH-M	(α/α)₆	8 48

GH-N	β-helix	28 49

GH-O	(α/α)₆	52 116

GH-P	(α/α)₆	127 146

GH-Q	(α/α)₆	94 149 161

GH-R	(β/α)₈	29 107

GH-S	(α/α)₆	144 162 192 193 194

GH-T	(β/α)₇	57 119

[1] Henrissat B (1991) A classification of glycosyl hydrolases based on amino-acid sequence similarities. Biochem. J. 280:309-316 [PMID : 1747104].

[2] Henrissat B, Bairoch A (1993) New families in the classification of glycosyl hydrolases based on amino- acid sequence similarities. Biochem. J. 293:781-788 [PMID : 8352747].

[3] Henrissat B, Bairoch A (1996) Updating the sequence-based classification of glycosyl hydrolases. Biochem. J. 316:695-696 [PMID : 8687420].

[4] Davies G, Henrissat B (1995) Structures and mechanisms of glycosyl hydrolases. Structure 3:853-859 [PMID : 8535779].

[5] Terwisscha van Scheltinga A, Armand S, Kalk KH, Isogai A, Henrissat B, Dijkstra BW (1995) Stereochemistry of chitin hydrolysis by a plant chitinase/lysozyme and x-ray structure of a complex with allosamidin. Evidence for substrate assisted catalysis. Biochemistry 34:15619-15623
[PMID : 7495789].

[6] Rajan SS, Yang X, Collart F, Yip VL, Withers SG, Varrot A, Thompson J, Davies GJ, Anderson WF (2004) Novel catalytic mechanism of glycoside hydrolysis based on the structure of an NAD+/Mn2+ -dependent phospho-alpha-glucosidase from Bacillus subtilis. Structure. 12:1619-1629
[PMID : 15341727].

[7] Liu QP, Sulzenbacher G, Yuan H, Bennett EP, Pietz G, Saunders K, Spence J, Nudelman E, Levery SB, White T, Neveu JM, Lane WS, Bourne Y, Olsson ML, Henrissat B, Clausen H (2007) Bacterial glycosidases for the production of universal red blood cells. Nature Biotechnol. 25:454-464
[PMID : 17401360].

Some glycoside hydrolases are multifunctional enzymes that contain catalytic domains that belong to different GH families.

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140	141	142	143	144	145	146	147	148	149	150	151	152	153	154	155	156	157	158	159	160
161	162	163	164	165	166	167	168	169	170	171	172	173	174	175	176	177	178	179	181	182	183	184	185	186	187	188	189	190	191	192	193	194	195

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140	141	142	143	144	145	146	147	148	149	150	151	152	153	154	155	156	157	158	159	160
161	162	163	164	165	166	167	168	169	170	171	172	173	174	175	176	177	178	179	181	182	183	184	185	186	187	188	189	190	191	192	193	194	195

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140

1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	28	29	30	31	32	33	34	35	36	37	38	39	40
41	42	43	44	45	46	47	48	49	50	51	52	53	54	55	56	57	58	59	60	61	62	63	64	65	66	67	68	69	70	71	72	73	74	75	76	77	78	79	80
81	82	83	84	85	86	87	88	89	90	91	92	93	94	95	96	97	98	99	100	101	102	103	104	105	106	107	108	109	110	111	112	113	114	115	116	117	118	119	120
121	122	123	124	125	126	127	128	129	130	131	132	133	134	135	136	137	138	139	140	141	142	143	144	145	146	147	148	149	150	151	152	153	154	155	156	157	158	159	160
161	162	163	164	165	166	167	168	169	170	171	172	173	174	175	176	177	178	179	181	182	183	184	185	186	187	188	189	190	191	192	193	194	195