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Document difference between IL-1Ra and IL-1 agonists has been observed on the side of the beta barrel on site B of the receptor binding site (see below). The Cα positions in this region (residues 84–94 in loop β7–β8) differ by 9.1 Å [26] in comparison with IL-1β. This region also contains Asn84, which is the site for at least two forms of N-linked glycosylation that occur in IL-1Ra in addition to the nonglycosylated form. Mutagenesis experiments have also http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_409.html (2 of 2) [4/5/2004 5:45:22 PM]
Document Figure 7 (a) Superposition of the Cα atoms of IL-1α, IL-1β, and IL-1Ra. (b) A common trefoil core based on the structural superposition of all the three IL-1 molecules. Page 410 identified this region and the surrounding area in IL-1β with a large receptor binding epitope encompassing the N and C termini of the protein as well as loops β4–β5 and β9–β10. The other postulated binding epitope (epitope A) is structurally conserved in IL-1Ra. Other differences in structure not related to any implicated biological structure are an extended 3 10 helix in residues 92–99 in IL-1Ra as opposed to a type-1 β turn found in IL-1β. F. Three-Dimensional Structure of Interleukin-1 Beta Converting Enzyme (ICE) As mentioned above, the processing of the different members of the IL-1 family is important to discovering their function and may also provide clues in the http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_410.html (1 of 2) [4/5/2004 5:45:50 PM]
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Structure-based Drug Design 14 Stru
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Document Figure 2 Schematic represe
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Document 8. Kaplan AH, Zack JA, Kni
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Document 60. Condra JH, Schleif WA,
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Document 74. Reddy RM, Varney MD, K
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Document 2 Structural Studies of HI
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Document Figure 1 (a) Chemical stru
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Document dine (3TC), and 2',3'-dide
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Document Figure Continued Page 45 r
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Document Figure 2 Ribbon diagrams o
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Document monophosphate analogs whic
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Document Analysis of various HIV-1
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Document Page 54 Table 2) [12,54].
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Document Page 56 It is also attract
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Document Table 3 HIV-1 RT Amino Aci
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Document ever, once an NNRTI is bou
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Document Page 61 now clear that the
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Document Page 63 most of the amino
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Document Page 65 cal properties of
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Document Page 67 Biochemical data s
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Document Page 69 determining the me
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Document Chris Tantillo. The work i
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Document Page 72 16. Goldman ME, Nu
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Document 30. Coffin JM. HIV populat
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Document 45. Majumadar C, Abbotts J
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Document reverse transcriptase inhi
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Document 75. Ring CS, Sun E, McKerr
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Document 89. Hughes SH, Arnold E, H
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Document 106. Cirino NM, Cameron CE
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Document 122. Marshall WS, Beaton G
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Document dine) and didanosine (dide
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Document 149. Craig JC, Duncan IB,
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Document 163. Lacey SF, Larder BA.
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Document Figure 1 Retroviral lifecy
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Document Figure 2 In vivo reactions
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Document Page 88 transfer (Figure 3
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Document Page 92 The role of the N-
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Document Figure 6 Molscript stereo
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Document Page 96 region in the HIV-
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Document day junction resolving enz
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Document -62° for HIV-1 integrase,
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Document Page 101 crystallized unde
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Document Figure 8 Molscript stereo
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Document proposed mechanisms. For e
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Document Page 106 on the same ring
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Document Page 108 mulate during tre
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Document when metals are bound. Fin
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Document cubation of phosphotyrosin
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Document 65. Gallay P, Swingler S,
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Document 4 Bradykinin Receptor Anta
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Document Page 121 Nearly all cells
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Document Page 123 were poorly satis
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Document Page 125 binding site on t
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Document Page 127 The des-Arg 9 for
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Document Page 129 tolerated by the
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Document receptor, it has not yet b
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Document Page 135 might be jointly
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Document Page 137 observed for the
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Document Figure 6 Rat and human B2
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Document Page 141 receptor with int
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Document Figure 9 Composition of te
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Document 16. Martorana PA, Kettenba
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Document 39. Mavunkel BJ, Lu Z, Kyl
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Document B. Pharmacology Figure 1 T
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Document We determined the structur
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Document Figure 3 Previously known
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Document large solvent channels and
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Document IV. Drug Design Progressio
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Document position eight from formin
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Document Table 1 Inhibition Data fo
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Document Page 166 As predicated, th
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Document References 1. Parks RE Jr.
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Document 17. Ealick SE, Rule SA, Ca
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Document 6 Structural Implications
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Document Figure 1 A ribbon model of
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Document Page 176 0.43 Å) as the c
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Document Page 178 studies show that
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Document Page 182 (SAR) model. The
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Document IX. S2' Interactions Page
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Document 7 Structure—Function Rel
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Document Important for the validity
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Document Figure 4 Amino acids impor
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Document III. Results and Discussio
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Document Page 202 269, and valine-2
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Document Figure 6 Structure of α h
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Document Page 205 enzyme and of phe
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Document Page 207 sure and the acti
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Document Page 214 viruses. Specific
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Document Figure 5 (a) Staurosporine
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Document protein kinase core is ess
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Document diverse ARIs have been sho
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Document Cyclotheonamide A (CtA), a
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Document Page 256 The discovery pro
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Document et al. [21]). Among these
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Document balance its pro- and antic
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Document Lys in the P1 position is
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Document 12 Polypeptide Modulators
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Document A. Chemical Modification P
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Document plasma. This may arise fro
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Document Table 1 Trypanosomal Targe
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Page 461 and 462: Document Figure 6 Stereoview of NAD
Page 463 and 464: Document Page 376 was recently solv
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Page 471 and 472: Document Because there are tens of
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Page 477 and 478: Document Figure 12 Predicted bindin
Page 479 and 480: Document Page 388 nosine proved to
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Page 483 and 484: Document 30. Kim H, Feil I, Verlind
Page 485 and 486: Document 49. Michels PAM, Hannaert
Page 487 and 488: Document 65. João HC, Williams RJP
Page 489 and 490: Document 84. Verlinde CLMJ, Hol WGJ
Page 491 and 492: Document 16 Progress in the Design
Page 493 and 494: Document Table 1 Known Three-Dimens
Page 495 and 496: Document Page 398 with growth hormo
Page 497 and 498: Document All effects of the IL-1 fa
Page 499 and 500: Document has a single membrane-span
Page 501 and 502: Document Figure 2 Structural alignm
Page 503 and 504: Document Page 405 strands constitut
Page 505 and 506: Document Figure 4 (a) Stereo diagra
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Page 511 and 512: Document Page 412 ture is unlike ot
Page 513 and 514: Document Figure 10 Schematic diagra
Page 515 and 516: Document Page 416 positions of the
Page 517 and 518: Document Figure 11 Functional resid
Page 519 and 520: Document Figure 13 The identified p
Page 521 and 522: Document B. Interleukin-1 Receptor
Page 523 and 524: Document Page 423 American Home Pro
Page 525 and 526: Document Page 425 Antinflammatory D
Page 527 and 528: Document Page 427 These aromatic di
Page 529 and 530: Document 5. Dinarello CA. On the Bi
Page 531 and 532: Document 21. Seckinger P, Lowenthal
Page 533 and 534: Document 39. Saurat JH, Schfferli J
Page 535 and 536: Document receptor antagonist into a
Page 537 and 538: Document 74. Bender PE, Lee JC., ed
Page 539 and 540: Document 102. Machin PJ, Osbond JM,
Page 541 and 542: Document 17 Structure and Functiona
Page 543 and 544: Document Table 1 Approval Indicatio
Page 545 and 546: Document Page 438 proteins. One pot
Page 547 and 548: Document II. Type IFNs A great deal
Page 549 and 550: Document Page 441 sequence of the m
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Page 553 and 554: Document Figure 4 Stereo view of IF
Page 555 and 556: Document Figure 5 Velcro-key model
Page 557 and 558: Document Figure 6 Proposed receptor
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Document Page 451 with the cytoplas
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Document Page 462 strains of influe
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Document Page 464 could not again b
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Document Page 471 molecules in the
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Document Page 476 nM, respectively.
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Document VI. Conclusion Page 480 It
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Document 64. Ward CW, Elleman TC, A
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Document Page 488 against most of t
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Document A. The Canyon Page 491 The
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Document Subsequent studies have sh
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Document Page 495 of the RNA and pr
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Document Figure 4 A ribbon diagram
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Document Figure 5 Some compounds wh
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Document Page 514 sis. Large number
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Document Acknowledgments Page 620 I
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Document 18. Sawyer TK. In: Peptide
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Document Med Biol 1991; 306:9-21; (
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Document Page 629 ML, Clare M, Decr
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Document Page 631 197. Musil D, Zuc
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Document son AH, Drummond AH, Huxle
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Document site, 52, 55, 61 triad, 24
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Document factors, 247 Combination t
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Document Cyclotheonamide A (CtA), 2
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Document D ddI, 152 tumour necrosis
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Document antistasin peptides, 281 c
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Document fragment-based programs, 5
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Document [Human immunodeficiency vi
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Document overview, 103-104, 108-109
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Document antagonistic activity, 416
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Document Kininogen, 119 high molecu
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Document RT inhibitor, 41, 56 Nonpe
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Document Phosphoglycerate kinase (P
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Document [Protease targets] serinyl
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