Hen Egg-White (HEW) Lysozyme

From Proteopedia

Revision as of 01:25, 31 March 2011

Discovery and Applications of Hen Egg-White Lysozyme

Lysozyme was the first enzyme whose X-ray structure was determined ^[1][2]. This shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a that fits into the cleft, labeling the sugar subsites A-F^[3]. Alternately click on and to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a . This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published ,^[4] in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a . In this of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the to the just toggle between the two green links.

3D Structures of Lysozyme

Lys

2x0a, 3iju, 3ijv, 3a8z, 2w1y, 2w1m, 2w1x, 2w1l, 3e3d, 3exd, 2zq3, 2zq4, 3b72, 3b6l, 2z12, 2z18, 2z19, 2vb1, 2hu3, 2hub, 2htx, 2hu1, 2yvb, 2epe, 2g4p, 2g4q, 2cgi, 2b5z, 2d4k, 2d91, 2f2n, 2fbb, 2c8o, 2c8p, 2a6u, 2aub, 2blx, 2bly, 2a7d, 2a7f, 1wtm, 1wtn, 1w6z, 1vdp, 1vdq, 1vds, 1vdt, 1ved, 1v7t, 1ps5, 2cds, 1lj3, 1lj4, 1lje, 1ljf, 1ljg, 1ljh, 1lji, 1ljj, 1ljk, 1jis, 1jit, 1jiy, 1jj0, 1jj1, 1jj3, 1iee, 1qio, 1f0w, 1f10, 1dpx, 1c10, 1qtk, 1lz8, 1lz9, 1bhz, 1bgi, 1bwh, 1bwi, 1bwj, 1bvx, 1hsw, 1hsx, 1lpi, 4lzt, 3lzt, 1aki, 1jpo, 1rfp, 193l, 194l, 5lym, 1lza, 3lyt, 4lyt, 5lyt, 6lyt, 2lzt, 1lzt, 1lzh, 2lzh, 7lyz, 1lyz, 2lyz, 3lyz, 4lyz, 5lyz, 6lyz - HEWL – chicken
1xei, 1xej, 1xek, 1uco, 1lma, 4lym – HEWL low hydration
1lsa, 1lsb, 1lsc, 1lsd, 1lse, 1lsf, 1lys – HEWL temperature influence
2lym, 3lym – HEWL pressure influence
132l – HEWL methylated
1rcm – HEWL 3 S-S form
2xbr, 2xbs- HEWL– Raman crystallography
2zwb, 1io5, 1lzn - HEWL– Neutron
1gxv, 1gxx, 1e8l - HEWL- NMR
2hs7, 2hso, 2hs9- HEWL– Powder diffraction
1ir7, 1ir8, 1ir9, 1ioq, 1ior, 1ios, 1iot, 1flq, 1flu, 1flw, 1fly, 1fn5, 1kxw, 1kxx, 1kxy, 1uia, 1uib, 1uic, 1uid, 1uie, 1uif, 1uig, 1uih, 1lsm, 1lsn, 1hel, 1hem, 1hen, 1heo, 1hep, 1heq, 1her – HEWL (mutant)
1lyo, 2lyo, 3lyo, 4lyo – HEWL cross-linked
1xft - tuLys – turkey - Powder diffraction
1jse, 1tew, 135l, 2lz2, 1lz2 – tuLys
3lz2 – tuLys - Laue
3ab6 – Lys + NAG3 – Hard clam
2x8r – Lys GH25 – Aspergillus fumigatus
3mgw – Lys G – Atlantic salmon
3gxk, 3gxr – Lys G + NAG – Atlantic cod
2fbd – HfLys 1
3cb7 – HfLys 2
2zij, 2zik, 2zil, 2nwd, 1iwt, 1iwu, 1iwv, 1iww, 1iwx, 1iwy, 1iwz, 1jwr, 1jsf, 1rex, 1lz1 – hLys – human
1w08, 1ix0, 1ioc, 1ip1, 1ip2, 1ip3, 1ip4, 1ip5, 1ip6, 1ip7, 1qsw, 1gev, 1gez, 1gf0, 1gf3, 1gf4, 1gf5, 1gf6, 1gf7, 1i1z, 1i20, 1i22, 1gfr, 1gft, 1gfu, 1gfv, 1gf8, 1gf9, 1gfa, 1gfe, 1gfg, 1gfh, 1gfj, 1gfk, 1inu, 1gdx, 1ge0, 1ge1, 1ge2, 1ge3, 1ge4, 1gdw, 1gaz, 1gb0, 1gb2, 1gb3, 1gb5, 1gb6, 1gb7, 1gb8, 1gb9, 1gbo, 1gbw, 1gbx, 1gby, 1gbz, 1gay, 1eq4, 1eq5, 1eqe, 1c7p, 1di3, 1di4, 1di5, 1c43, 1c45, 1c46, 1ckg, 1cj6, 1cj7, 1cj8, 1cj9, 1ckc, 1ckd, 1ckf, 1ckh, 1b5z, 1b70, 1b7q, 1b7r, 1b7s, 1b7l, 1b7m, 1b7n, 1b7p, 1b5u, 1b5v, 1b5w, 1b5x, 1b5y, 1bb3, 1bb4, 2bqa, 2bqb, 2bqc, 2bqd, 2bqe, 2bqf, 2bqg, 2bqh, 2bqi, 2bqj, 2bqk, 2bql, 2bqm, 2bqn, 2bqo, 2mea, 2meb, 2mec, 2med, 2mee, 2mef, 2meg, 2meh, 2mei, 1wqm, 1wqn, 1wqo, 1wqp, 1wqq, 1wqr, 2heb, 2hea, 2hec, 2hed, 2hee, 2hef, 1jka, 1jkb, 1jkc, 1jkd, 1loz, 1lyy, 1oua, 1oub, 1ouc, 1oud, 1oue, 1ouf, 1oug, 1ouh, 1oui, 1ouj, 207l, 208l , 1yam, 1yan, 1yao, 1yap, 1yaq, 1lmt, 1lhh, 1lhi, 1lhj, 1lhk, 1lhl, 133l, 134l, 1lz4, 1lz5, 1lz6, 1laa, 1tay, 1tby, 1tcy, 1tdy, 2lhm, 3lhm – hLys (mutant)
1iy3, 1iy4 – hLys - NMR
2z2f – Lys – Bovine
2cwi, 1el1, 1qqy – dLys - dog
2z2e – dLys (mutant)
1i56 – dLys – NMR
2dqa – Lys – Tapes japonica
2gv0 – Lys – Soft-shelled turtle
1ivm – mLys M – NMR – mouse
1jfx – Lys – Streptomyces coelicolor
1gd6 – Lys – Bombyx mori
1jug – Lys – Echidna
1dkj – BqLys – Bobwhite quail
2ihl – Lys – Japanese quail
1gbs – BsLys – Black swan
1lmn – RtLys – Rainbow trout
2eql – Lys – horse
1ghl – phLys – pheasant
1hhl – GfLys – Guinea fowl
1lhm – Lys (mutant) – yeast

Lys small molecules complexes

3fe0, 2d4i, 2d4j, 1v7s - HEWL+ D2O
3m3u – HEWL Trp fluorescence
2xjw - HEWL + CO
1hf4, 1lks – HEWL + NO3
3a34, 3ems - HEWL + arginine
2xth – cLys + inhibitor K2PtBr6
3a90, 3a91, 3a92, 3a93, 3a94, 3a95, 3a96, 3kam, 2pc2, 2bpu, 1t3p, 1h87 – HEWL + rare earth
2d6b, 2hg0, 1vat, 1gwd, 1b2k, 1lkr, 1azf, 8lyz- HEWL+ halogen
1vat - HEWL + Xe
1n4f - HEWL + As
2i6z - HEWL + Pt drug
2zyp - HEWL + poly (allyl amine)
2f30, 2f4a – HEWL + urea derivative
2f4g, 1ykx, 1yky, 1ykz, 1yl0, 1yl1, 1z55 - HEWL + alcohol
1dpw – HEWL + MPD
1lcn – HEWL + SCN
2zxs - HEWL with glycine-amide
2h9j, 2h9k, 1yik, 1yil - HEWL + cyclam derivative
1b0d – HEWL + p-toluene-sulfonate
2q0m - HEWL + tricarbonylmanganese
2war – HEWL (mutant) + chitopentaose
2h5z – HfLys 1 + chitotetraose – House fly
1hnl – hLys + glutathione
1dkk – BqLys + NO3

Lys complex with glucoside

3a3q – HEWL (mutant) + NAG
1sf4, 1sf6, 1sf7, 1sfb, 1sfg, 1ja2, 1ja4, 1ja6, 1ja7 – HEWL + NAG oligosaccharide – Powder diffraction
1ubz, 1d6p, 1d6q, 1bb5 – hLys (mutant) + glycoside
1uc0, 1re2, 1rem, 1rey, 1rez, 1lzr, 1lzs - hLys + glycoside
1ljn, 1jef, 1lzy – tuLys + glycoside
1h6m, 1at5, 1at6, 1lzb, 1lzc, 1lzd, 1lze, 1lzg, 1hew – HEWL + glycoside
1lsy, 1lsz - HEWL (mutant) + glycoside
1bb6, 1bb7 – RtLys + glycoside
1lmc – RtLys + bulgecin
1lmo, 1lmp, 1lmq – RtLys + glucoside
1lsp – BsLys + bulgecin
153l, 154l – Lys +glucoside – goose

Phage Lys

2oe4, 2oe7, 2oe9, 2oea, 1swz, 1cx6, 1qtc, 1qtd, 1qth, 1qsb, 1qs5, 1qs9, 1qtb, 256l, 206l, 167l, 168l, 169l, 170l, 171l, 172l, 173l, 174l, 175l, 176l, 177l, 178l, 181l, 182l, 183l, 184l, 185l, 186l, 187l, 188l, 1nhb, 137l, 216l, 152l, 149l, 150l, 151l, 1lyd, 2lzm - T4Lys – Enterobacteria phage T4
138l – T4Lys cross-linked
4lzm, 5lzm, 6lzm, 7lzm – T4Lys ionic strength
3l2x, 3k2r, 3g3v, 3g3w, 3g3x, 2q9d, 2q9e, 2igc, 2ntg, 2nth, 2ou8, 2ou9, 1zur, 1zwn, 1zyt, 2cuu, 2a4t – T4Lys (mutant) spin labeled
3l64, 3hwl, 3jr6, 3gui, 3c7w, 3c7y, 3c7z, 3c80, 3c81, 3c82, 3c83, 3c8q, 3c8r, 3c8s, 3cdo, 3cdq, 3cdr, 3cdt, 3cdv, 3f8v, 3f9l, 3fa0, 3fad, 3fi5, 3dke, 3dmv, 2o4w, 2o79, 2o7a, 2huk, 2hul, 2hum, 2b7x, 2b6t, 2b6w, 2b6x, 2b6y, 2b6z, 2b70, 2b72, 2b73, 2b74, 2b75, 1sx7, 1swy, 1sx2, 1t6h, 1ssw, 1ssy, 1t8f, 1t8g, 1t8a, 1t97, 1p56, 1p5c, 1p2l, 1p2r, 1p36, 1p37, 1p3n, 1p46, 1p64, 1p6y, 1p7s, 1pqd, 1pqi, 1pqj, 1pqk, 1pqm, 1pqo, 1oyu, 1ks3, 1kw5, 1kw7, 1ky0, 1ky1, 1l0j, 1l0k, 1lw9, 1lwg, 1lwk, 1lpy, 1llh, 1lgu, 1li6, 1jtm, 1jtn, 1jqu, 1kni, 1g06, 1g07, 1g0g, 1g0j, 1g0k, 1g0l, 1g0m, 1g0p, 1g0q, 1g1v, 1g1w, 1i6s, 257l, 258l, 260l, 1epy, 1b6i, 1cu6, 1d9w, 1ctw, 1cu0, 1cu2, 1cu3, 1cu5, 1cv1, 1cv4, 1cv5, 1cv6, 1cvk, 1cx7, 1d2w, 1d2y, 1d3f, 1d3j, 1d3m, 1d3n, 1cv3, 1qt3, 1qt4, 1qt5, 1qt6, 1qt7, 1qt8, 1qtv, 1qtz, 1qud, 1qug, 1quh, 1quo, 1qsq, 261l, 262l, 259l, 220l, 222l, 223l, 225l, 226l, 227l, 228l, 229l, 235l, 236l, 237l, 238l, 239l, 240l, 241l, 242l, 243l, 244l, 245l, 246l, 247l, 248l, 249l, 250l, 251l, 252l, 253l, 254l, 255l, 230l, 231l, 232l, 233l, 234l, 209l, 210l, 211l, 212l, 213l, 214l, 215l, 218l, 219l, 180l, 195l, 196l, 197l, 198l, 199l, 200l, 190l, 191l, 192l, 189l, 155l, 156l, 157l, 158l, 159l, 160l, 161l, 162l, 163l, 164l, 165l, 166l, 129l, 130l, 131l, 140l, 141l, 142l, 143l, 144l, 145l, 146l, 147l, 201l, 205l, 221l, 224l, 102l, 103l, 104l, 107l, 108l, 109l, 110l, 111l, 112l, 113l, 114l, 115l, 118l, 119l, 120l, 122l, 123l, 125l, 126l, 127l, 128l, 1dya, 1dyb, 1dyc, 1dyd, 1dye, 1dyf, 1dyg, 1l00, 1l85, 1l86, 1l87, 1l88, 1l89, 1l90, 1l91, 1l92, 1l93, 1l94, 1l95, 1l96, 1l97, 1l98, 1l99, 1lye, 1lyf, 1lyg, 1lyh, 1lyi, 1lyj, 217l, 1tla, 1l77, 1l79, 1l80, 1l81, 1l82, 2l78, 1l36, 1l37, 1l38, 1l39, 1l40, 1l41, 1l42, 1l43, 1l44, 1l45, 1l46, 1l47, 1l48, 1l49, 1l50, 1l51, 1l52, 1l53, 1l54, 1l55, 1l56, 1l57, 1l58, 1l59, 1l60, 1l61, 1l62, 1l63, 1l64, 1l65, 1l66, 1l67, 1l68, 1l69, 1l70, 1l71, 1l72, 1l73, 1l74, 1l75, 1l76, 1l17, 1l18, 1l19, 1l20, 1l21, 1l22, 1l23, 1l24, 1l25, 1l26, 1l27, 1l28, 1l29, 1l30, 1l31, 1l32, 1l33, 1l34, 1l35, 3lzm, 1l01, 1l02, 1l03, 1l04, 1l05, 1l06, 1l07, 1l08, 1l09, 1l10, 1l11, 1l12, 1l13, 1l14, 1l15, 1l16 – T4Lys (mutant)
1c60, 1c61, 1c62, 1c63, 1c64, 1c65, 1c66, 1c67, 1c68, 1c69, 1c6a, 1c6b, 1c6c, 1c6d, 1c6e, 1c6f, 1c6g, 1c6h, 1c6i, 1c6j, 1c6k, 1c6l, 1c6m, 1c6n, 1c6p, 1c6q, 1c6t - T4Lys (mutant) + noble gas
3ht6, 3ht7, 3ht8, 3ht9, 3htb, 3hu8, 3huq, 3guj, 3guk, 3gul, 3gum, 3gun, 3guo, 3gup, 3dmx, 3dmz, 3dn0, 3dn1, 3dn2, 3dn3, 3dn4, 3dn6, 3dn8, 3dna, 2rb1, 2ray, 2raz, 2rb0, 2rb2, 2rbn, 2rbo, 2rbq, 2rbr, 2rbs, 2oty,2otz, 1owy, 1owz, 1ov5, 1ov7, 1ovh, 1ovj, 1ovk, 1lgw, 1lgx, 1li2, 1li3, 1l83, 1l84 – T4Lys (mutant) + benzene derivative
3htd, 3htf, 3htg, 3hu9, 3hua, 3huk, 3hh3, 3hh4, 3hh5, 3hh6, 2rbp, 2ou0, 2f2q, 2f32, 2f47, 1xep – T4Lys (mutant) + inhibitor
148l - T4Lys (mutant) + glucoside
3d3d, 1d9u – lamLys + chitohexasaccharide
1am7 – lamLys - Enterobacteria phage λ
2anv, 2anx – Lys (mutant)]] - Enterobacteria phage p22
1xjt, 1xju - Lys - Enterobacteria phage p1
1lba - T7Lys - Enterobacteria phage T7

Lys protein complex

3m18, 3g3a, 3g3b - HEWL + Variable lymphocyte receptor – Marine lamprey
3a67, 3a6b, 3a6c, 2yss, 2eiz, 2dqc, 2dqd, 2dqe, 2dqf, 2dqg, 2dqh, 2dqi, 2dqj, 1j1o, 1j1p, 1j1x, 1ic4, 1ic5, 1ic7 – HEWL + mLys antibody HYHEL-10 (mutant)
1xgp, 1xgq, 1xgr, 1xgt, 1xgu – HEWL + mLys antibody HYHEL-63
3d9a, 2eks, 1ua6, 1c08, 3hfm – HEWL + mLys antibody HYHEL-10
1uac - tuLys C + mLys antibody HYHEL-10
1yqv, 2iff – HEWL + mLys antibody HYHEL-5
1bql – BqLys + mLys antibody HYHEL-5
1ndg – HEWL + mLys antibody HYHEL-8
1ndm – HEWL + mLys antibody HYHEL-26
1dqj - HEWL + mLys antibody HYHEL-63
1nby, 1nbz – HEWL (mutant) + mLys antibody HYHEL-63
1g7h, 1g7i, 1g7j, 1g7l, 1g7m, 1kip, 1kiq, 1kir – HEWL + mAnti-HEWL monoclonal antibody (mutant)
1mlc, 1vfb - HEWL + mIGG1-κ D44.1 FAB
1a2y - HEWL (mutant) + mIGG1-κ D1.3 FV
1fdl - HEWL + mIGG1-κ D1.3 FAB
1jhl – phLys + mIGG1-κ D11.15 FV
1fbi – GfLys + mIGG1 F9.13.7 FAB
2znw, 2znx – HEWL + hSCFV10 antibody
1bvk - HEWL + hAnti Lys FV antibody
1dzb – tuLys + mSCFV 1F9
1zv5, 1zvh, 1zvy, 1zmy, 1ri8, 1rjc, 1xfp, 1jtp, 1jtt, 1jto, 1mel - HEWL + cAntibody heavy chain domain – camel
1op9 - hLys C + cAntibody heavy chain domain
3otp – HEWL + EcProtease DO – Escherichia coli
3f6z - HEWL + MLIC – Pseudomonas aeruginosa
3eba – hLys C + hCABHUL6
2qb0, 2qar – T4Lys/E80 TELSAM domain
2i25, 2i26 - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark
1sq2, 1t6v – HEWL +NsNew Antigen receptor variable domain
1gpq – HEWL + EcInhibitor of Vertebrate Lys
1aro – T7Lys + T7 RNA polymerase

Some Useful External Links

Lysozyme

Retaining Glycoside Hydrolases

References

1. ↑ Johnson LN, Phillips DC. Structure of some crystalline lysozyme-inhibitor complexes determined by X-ray analysis at 6 Angstrom resolution. Nature. 1965 May 22;206(986):761-3. PMID:5840126
2. ↑ Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)
3. ↑ coordinates of the model kindly provided by Louise Johnson
4. ↑ Vocadlo DJ, Davies GJ, Laine R, Withers SG. Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate. Nature. 2001 Aug 23;412(6849):835-8. PMID:11518970 doi:10.1038/35090602