2rmp
From Proteopedia
(New page: 200px<br /><applet load="2rmp" size="450" color="white" frame="true" align="right" spinBox="true" caption="2rmp, resolution 2.7Å" /> '''RMP-PEPSTATIN A COMPL...) |
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| - | [[Image:2rmp.jpg|left|200px]]<br /><applet load="2rmp" size=" | + | [[Image:2rmp.jpg|left|200px]]<br /><applet load="2rmp" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2rmp, resolution 2.7Å" /> | caption="2rmp, resolution 2.7Å" /> | ||
'''RMP-PEPSTATIN A COMPLEX'''<br /> | '''RMP-PEPSTATIN A COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Crystals of Rhizomucor miehei aspartic proteinase (RMP) complexed with | + | Crystals of Rhizomucor miehei aspartic proteinase (RMP) complexed with pepstatin A grew in the orthorhombic space group P212121 and were isomorphous to native RMP crystals. The unit-cell dimensions are a = 41.52, b = 50.82, c = 172.71 A. There is one RMP-pepstatin A complex per asymmetric unit. The structure of the RMP-pepstatin A complex has been refined to a crystallographic R value of 19.3% and an Rfree value of 28.0% at 2.7 A resolution. A pepstatin A molecule fits into the large substrate-binding cleft between the two domains of RMP in an extended conformation up to the alanine residue at the P2' position. The dipeptide analogue statine residue at the P3'-P4' position forms an inverse gamma-turn (P3'-P1') with the statine residue at the P1-P1' position and its leucyl side chain binds back into the S1' subsite. The inhibitor interacts with the residues of the substrate-binding pocket by both hydrogen bonds and hydrophobic interactions. The hydroxyl group of the statine residue at the P1-P1' position forms hydrogen bonds with both catalytic aspartate residues (Asp38 and Asp237). This conformation mimics the expected transition state of the enzyme-substrate interaction. The binding of the inhibitor to the enzyme does not produce large distortions of the active site. No domain movement was observed compared with the native enzyme structure. However, the surface-flap region (residues 82-88) undergoes a conformational change, moving toward the inhibitor and becoming rigid owing to the formation of hydrogen bonds with the inhibitor. B-factor calculations of the two domains suggest that the C-terminal domain becomes more rigid in the complex than in the native structure. |
==About this Structure== | ==About this Structure== | ||
| - | 2RMP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhizomucor_miehei Rhizomucor miehei] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Mucorpepsin Mucorpepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.23 3.4.23.23] Full crystallographic information is available from [http:// | + | 2RMP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhizomucor_miehei Rhizomucor miehei] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Mucorpepsin Mucorpepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.23 3.4.23.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RMP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rhizomucor miehei]] | [[Category: Rhizomucor miehei]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Quail, J | + | [[Category: Quail, J W.]] |
[[Category: Yang, J.]] | [[Category: Yang, J.]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: pepstatin a]] | [[Category: pepstatin a]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:48:32 2008'' |
Revision as of 16:48, 21 February 2008
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RMP-PEPSTATIN A COMPLEX
Overview
Crystals of Rhizomucor miehei aspartic proteinase (RMP) complexed with pepstatin A grew in the orthorhombic space group P212121 and were isomorphous to native RMP crystals. The unit-cell dimensions are a = 41.52, b = 50.82, c = 172.71 A. There is one RMP-pepstatin A complex per asymmetric unit. The structure of the RMP-pepstatin A complex has been refined to a crystallographic R value of 19.3% and an Rfree value of 28.0% at 2.7 A resolution. A pepstatin A molecule fits into the large substrate-binding cleft between the two domains of RMP in an extended conformation up to the alanine residue at the P2' position. The dipeptide analogue statine residue at the P3'-P4' position forms an inverse gamma-turn (P3'-P1') with the statine residue at the P1-P1' position and its leucyl side chain binds back into the S1' subsite. The inhibitor interacts with the residues of the substrate-binding pocket by both hydrogen bonds and hydrophobic interactions. The hydroxyl group of the statine residue at the P1-P1' position forms hydrogen bonds with both catalytic aspartate residues (Asp38 and Asp237). This conformation mimics the expected transition state of the enzyme-substrate interaction. The binding of the inhibitor to the enzyme does not produce large distortions of the active site. No domain movement was observed compared with the native enzyme structure. However, the surface-flap region (residues 82-88) undergoes a conformational change, moving toward the inhibitor and becoming rigid owing to the formation of hydrogen bonds with the inhibitor. B-factor calculations of the two domains suggest that the C-terminal domain becomes more rigid in the complex than in the native structure.
About this Structure
2RMP is a Single protein structure of sequence from Rhizomucor miehei with as ligand. Active as Mucorpepsin, with EC number 3.4.23.23 Full crystallographic information is available from OCA.
Reference
Structure of the Rhizomucor miehei aspartic proteinase complexed with the inhibitor pepstatin A at 2.7 A resolution., Yang J, Quail JW, Acta Crystallogr D Biol Crystallogr. 1999 Mar;55(Pt 3):625-30. PMID:10089458
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