1gnm
From Proteopedia
(New page: 200px<br /> <applet load="1gnm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gnm, resolution 2.3Å" /> '''HIV-1 PROTEASE MUTAN...) |
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| - | [[Image:1gnm.gif|left|200px]]<br /> | + | [[Image:1gnm.gif|left|200px]]<br /><applet load="1gnm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gnm" size=" | + | |
caption="1gnm, resolution 2.3Å" /> | caption="1gnm, resolution 2.3Å" /> | ||
'''HIV-1 PROTEASE MUTANT WITH VAL 82 REPLACED BY ASP (V82D) COMPLEXED WITH U89360E (INHIBITOR)'''<br /> | '''HIV-1 PROTEASE MUTANT WITH VAL 82 REPLACED BY ASP (V82D) COMPLEXED WITH U89360E (INHIBITOR)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Crystal structures of the protease of human immunodeficiency virus type 1 | + | Crystal structures of the protease of human immunodeficiency virus type 1 (HIV-1) and two mutant proteases, V82D and V82N, have been determined. In all three cases the enzyme forms a complex with the peptidic inhibitor U-89360E. All structures have been determined to 2.3 A resolution and have satisfactory agreement factors: 0.173 for wild type, 0.175 for V82D, and 0.182 for V82N. Comparison of the three crystal structures provides explanations which are consistent with the known kinetic properties of these mutant enzymes with the U-89360E inhibitor [Lin, Y., Lin, X., Hong, L., Foundling, S., Heinrikson, R. L., Thaisrivongs, S., Leelamanit, W., Raterman, D., Shah, M., Dunn, B.M., & Tang, J. (1995) Biochemistry 34, 1143-1152]. Unfavorable van der Waals interactions between the inhibitor and the mutated side chains at position 82 are consistent with diminished affinity for the inhibitor by the mutant enzymes. If a mutation is potentially resistant to an inhibitor, the mutant enzyme should not only have an increased Ki for the inhibitor but should also preserve considerable catalytic capability. The V82D mutant possesses these qualities. In the V82D crystal structure, a water molecule, which connects the protease flap to the inhibitor, is missing or of low occupancy. Absence of this bridge may be important in determining catalytic capability. Moreover, mutation at position 82 induces change in two polypeptide backbone regions, 35-41 and 67-68, which may be related to protease flap mobility. |
==About this Structure== | ==About this Structure== | ||
| - | 1GNM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with U0E as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http:// | + | 1GNM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=U0E:'>U0E</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GNM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Foundling, S.]] | [[Category: Foundling, S.]] | ||
| - | [[Category: Hartsuck, J | + | [[Category: Hartsuck, J A.]] |
[[Category: Hong, L.]] | [[Category: Hong, L.]] | ||
[[Category: Tang, J.]] | [[Category: Tang, J.]] | ||
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[[Category: u-89360e]] | [[Category: u-89360e]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:51:58 2008'' |
Revision as of 10:51, 21 February 2008
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HIV-1 PROTEASE MUTANT WITH VAL 82 REPLACED BY ASP (V82D) COMPLEXED WITH U89360E (INHIBITOR)
Overview
Crystal structures of the protease of human immunodeficiency virus type 1 (HIV-1) and two mutant proteases, V82D and V82N, have been determined. In all three cases the enzyme forms a complex with the peptidic inhibitor U-89360E. All structures have been determined to 2.3 A resolution and have satisfactory agreement factors: 0.173 for wild type, 0.175 for V82D, and 0.182 for V82N. Comparison of the three crystal structures provides explanations which are consistent with the known kinetic properties of these mutant enzymes with the U-89360E inhibitor [Lin, Y., Lin, X., Hong, L., Foundling, S., Heinrikson, R. L., Thaisrivongs, S., Leelamanit, W., Raterman, D., Shah, M., Dunn, B.M., & Tang, J. (1995) Biochemistry 34, 1143-1152]. Unfavorable van der Waals interactions between the inhibitor and the mutated side chains at position 82 are consistent with diminished affinity for the inhibitor by the mutant enzymes. If a mutation is potentially resistant to an inhibitor, the mutant enzyme should not only have an increased Ki for the inhibitor but should also preserve considerable catalytic capability. The V82D mutant possesses these qualities. In the V82D crystal structure, a water molecule, which connects the protease flap to the inhibitor, is missing or of low occupancy. Absence of this bridge may be important in determining catalytic capability. Moreover, mutation at position 82 induces change in two polypeptide backbone regions, 35-41 and 67-68, which may be related to protease flap mobility.
About this Structure
1GNM is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
Reference
Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases., Hong L, Treharne A, Hartsuck JA, Foundling S, Tang J, Biochemistry. 1996 Aug 20;35(33):10627-33. PMID:8718851
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