1z1r

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[[Image:1z1r.gif|left|200px]]
[[Image:1z1r.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1z1r |SIZE=350|CAPTION= <scene name='initialview01'>1z1r</scene>, resolution 1.85&Aring;
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The line below this paragraph, containing "STRUCTURE_1z1r", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=HBH:2-[(8S,11S)-11-{(1R)-1-HYDROXY-2-[ISOPENTYL(PHENYLSULFONYL)AMINO]ETHYL}-6,9-DIOXO-2-OXA-7,10-DIAZABICYCLO[11.2.2]HEPTADECA-1(15),13,16-TRIEN-8-YL]ACETAMIDE'>HBH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_1z1r| PDB=1z1r | SCENE= }}
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|RELATEDENTRY=[[1b6n|1B6N]], [[1b6j|1B6J]], [[1b6o|1B6O]], [[1b6l|1B6L]], [[1b6k|1B6K]], [[1b6m|1B6M]], [[1b6p|1B6P]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1r OCA], [http://www.ebi.ac.uk/pdbsum/1z1r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z1r RCSB]</span>
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}}
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'''HIV-1 protease complexed with Macrocyclic peptidomimetic inhibitor 2'''
'''HIV-1 protease complexed with Macrocyclic peptidomimetic inhibitor 2'''
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==About this Structure==
==About this Structure==
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1Z1R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. This structure supersedes the now removed PDB entry 1B6O. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1R OCA].
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1Z1R is a [[Single protein]] structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1b6o 1b6o]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1R OCA].
==Reference==
==Reference==
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[[Category: Schindeler, A.]]
[[Category: Schindeler, A.]]
[[Category: Wickramasinghe, W A.]]
[[Category: Wickramasinghe, W A.]]
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[[Category: hiv1 protease]]
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[[Category: Hiv1 protease]]
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[[Category: macrocyclic inhibitor]]
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[[Category: Macrocyclic inhibitor]]
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[[Category: peptidomimetic inhibitor]]
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[[Category: Peptidomimetic inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:04:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:27:50 2008''
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Revision as of 14:05, 3 May 2008

Image:1z1r.gif

Template:STRUCTURE 1z1r

HIV-1 protease complexed with Macrocyclic peptidomimetic inhibitor 2


Overview

High-resolution crystal structures are described for seven macrocycles complexed with HIV-1 protease (HIVPR). The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIVPR. Appended to each macrocycle is a transition state isostere and either an acyclic peptide, nonpeptide, or another macrocycle. These cyclic analogues are potent inhibitors of HIVPR, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of HIVPR via the same interactions. Each macrocycle is restrained to adopt a beta-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIVPR. A bicyclic inhibitor binds similarly through its secondary amine that lies between its component N-terminal and C-terminal macrocycles. In contrast, the corresponding tertiary amine of the N-terminal macrocycles does not interact with the catalytic aspartates. The amine-aspartate interaction induces a 1.5 A N-terminal translation of the inhibitors in the active site and is accompanied by weakened interactions with a water molecule that bridges the ligand to the enzyme, as well as static disorder in enzyme flap residues. This flexibility may facilitate peptide cleavage and product dissociation during catalysis. Proteases [Aba67,95]HIVPR and [Lys7,Ile33,Aba67,95]HIVPR used in this work were shown to have very similar crystal structures.

About this Structure

1Z1R is a Single protein structure. This structure supersedes the now removed PDB entry 1b6o. Full crystallographic information is available from OCA.

Reference

Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease., Martin JL, Begun J, Schindeler A, Wickramasinghe WA, Alewood D, Alewood PF, Bergman DA, Brinkworth RI, Abbenante G, March DR, Reid RC, Fairlie DP, Biochemistry. 1999 Jun 22;38(25):7978-88. PMID:10387041 Page seeded by OCA on Sat May 3 17:04:59 2008

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