5lab - Revision history

OCA at 07:48, 7 February 2024

2024-02-07T07:48:08Z

← Older revision		Revision as of 07:48, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LAB FirstGlance]. <br>		<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LAB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.34Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [https://pdbe.org/5lab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [https://www.ebi.ac.uk/pdbsum/5lab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [https://pdbe.org/5lab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [https://www.ebi.ac.uk/pdbsum/5lab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.		[https://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Long-range pseudo-contact NMR shifts (PCSs) provide important restraints for the structure refinement of proteins when a paramagnetic metal center is present, either naturally or introduced artificially. Here we show that ab initio quantum-chemical methods and a modern version of the Kurland-McGarvey approach for paramagnetic NMR (pNMR) shifts in the presence of zero-field splitting (ZFS) together provide accurate predictions of all PCSs in a metalloprotein (high-spin cobalt-substituted MMP-12 as a test case). Computations of 314 (13) C PCSs using g- and ZFS tensors based on multi-reference methods provide a reliable bridge between EPR-parameter- and susceptibility-based pNMR formalisms. Due to the high sensitivity of PCSs to even small structural differences, local structures based either on X-ray diffraction or on various DFT optimizations could be evaluated critically by comparing computed and experimental PCSs. Many DFT functionals provide insufficiently accurate structures. We also found the available 1RMZ PDB X-ray structure to exhibit deficiencies related to binding of a hydroxamate inhibitor. This has led to a newly refined PDB structure for MMP-12 (5LAB) that provides a more accurate coordination arrangement and PCSs.

	Pseudo-Contact NMR Shifts over the Paramagnetic Metalloprotein CoMMP-12 from First Principles.,Benda L, Mares J, Ravera E, Parigi G, Luchinat C, Kaupp M, Vaara J Angew Chem Int Ed Engl. 2016 Nov 14;55(47):14713-14717. doi: , 10.1002/anie.201608829. Epub 2016 Oct 26. PMID:27781358<ref>PMID:27781358</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 5lab" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Matrix metalloproteinase 3D structures\|Matrix metalloproteinase 3D structures]]		*[[Matrix metalloproteinase 3D structures\|Matrix metalloproteinase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:31, 22 March 2023

2023-03-22T07:31:02Z

← Older revision		Revision as of 07:31, 22 March 2023
Line 3:		Line 3:
	<StructureSection load='5lab' size='340' side='right'caption='[[5lab]], [[Resolution\|resolution]] 1.34Å' scene=''>		<StructureSection load='5lab' size='340' side='right'caption='[[5lab]], [[Resolution\|resolution]] 1.34Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5LAB FirstGlance]. <br>		<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LAB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [https://pdbe.org/5lab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [https://www.ebi.ac.uk/pdbsum/5lab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [~~http~~://pdbe.org/5lab PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5lab PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN]] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.		[https://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	~~The structures of the catalytic domain of matrix metalloproteinase 12 in the presence of acetohydroxamic acid and N~~-~~isobutyl~~-~~N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid have been solved by x-ray diffraction in~~ the ~~crystalline state at 1~~.~~0 and 1.3~~-~~A resolution, respectively,~~ and ~~compared with~~ the ~~previously published x~~-~~ray structure at 1.2-A resolution of~~ the ~~adduct with batimastat. The structure~~ of ~~the N~~-~~isobutyl~~-N-[4-~~methoxyphenylsulfonyl]glycyl hydroxamic acid adduct has been solved by NMR in solution~~. ~~The three x~~-~~ray structures~~ and ~~the solution structure are similar but not identical to one another, the differences being sizably higher in the loops. We propose that many of the loops show a dynamical behavior in solution~~ on a variety of time scales. Different conformations of some flexible regions of the protein can be observed as "frozen" in different crystalline environments. The mobility in solution studied by NMR reveals conformational equilibria in accessible time scales, i.e., from 10(-~~5) s to ms~~ and ~~more~~. ~~Averaging~~ of ~~some residual dipolar couplings is consistent with further motions down~~ to ~~10(-9) s. Finally~~, local ~~thermal motions of each frozen conformation in the crystalline state at 100 K correlate well with local motions~~ on ~~the picosecond time scale~~. ~~Flexibility/conformational heterogeneity in crucial parts of~~ the ~~catalytic domain is a rule rather than an exception in matrix metalloproteinases, and its extent may be underestimated by inspection of one x~~-ray structure. ~~Backbone flexibility may play~~ a ~~role in the difficulties encountered in the design of selective inhibitors, whereas it may be~~ a ~~requisite for substrate binding~~ and ~~broad substrate specificity~~.		Long-range pseudo-contact NMR shifts (PCSs) provide important restraints for the structure refinement of proteins when a paramagnetic metal center is present, either naturally or introduced artificially. Here we show that ab initio quantum-chemical methods and a modern version of the Kurland-McGarvey approach for paramagnetic NMR (pNMR) shifts in the presence of zero-field splitting (ZFS) together provide accurate predictions of all PCSs in a metalloprotein (high-spin cobalt-substituted MMP-12 as a test case). Computations of 314 (13) C PCSs using g- and ZFS tensors based on multi-reference methods provide a reliable bridge between EPR-parameter- and susceptibility-based pNMR formalisms. Due to the high sensitivity of PCSs to even small structural differences, local structures based either on X-ray diffraction or on various DFT optimizations could be evaluated critically by comparing computed and experimental PCSs. Many DFT functionals provide insufficiently accurate structures. We also found the available 1RMZ PDB X-ray structure to exhibit deficiencies related to binding of a hydroxamate inhibitor. This has led to a newly refined PDB structure for MMP-12 (5LAB) that provides a more accurate coordination arrangement and PCSs.

	~~Conformational variability of matrix metalloproteinases: beyond a single 3D structure~~.,~~Bertini I, Calderone V~~, ~~Cosenza M~~, ~~Fragai M~~, ~~Lee YM~~, Luchinat C, ~~Mangani S~~, ~~Terni B, Turano P Proc Natl Acad Sci U S A~~. ~~2005 Apr 12~~;~~102~~(15):~~5334~~-9. Epub ~~2005 Apr 4~~. PMID:~~15809432~~<ref>PMID:~~15809432~~</ref>		Pseudo-Contact NMR Shifts over the Paramagnetic Metalloprotein CoMMP-12 from First Principles.,Benda L, Mares J, Ravera E, Parigi G, Luchinat C, Kaupp M, Vaara J Angew Chem Int Ed Engl. 2016 Nov 14;55(47):14713-14717. doi: , 10.1002/anie.201608829. Epub 2016 Oct 26. PMID:27781358<ref>PMID:27781358</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
Line 27:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Macrophage elastase]]~~		[[Category: Calderone V]]
	[[Category: Calderone, V]]		[[Category: Luchinat C]]
	[[Category: Luchinat, C]]		[[Category: Ravera E]]
	[[Category: Ravera, E]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: Hydrolase mmp-12~~]]

OCA at 07:04, 5 August 2020

2020-08-05T07:04:24Z

← Older revision		Revision as of 07:04, 5 August 2020
Line 1:		Line 1:

	==Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor NNGH==		==Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor NNGH==
	<StructureSection load='5lab' size='340' side='right' caption='[[5lab]], [[Resolution\|resolution]] 1.34Å' scene=''>		<StructureSection load='5lab' size='340' side='right'caption='[[5lab]], [[Resolution\|resolution]] 1.34Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5LAB FirstGlance]. <br>		<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LAB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [http://pdbe.org/5lab PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [http://www.ebi.ac.uk/pdbsum/5lab PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [http://pdbe.org/5lab PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [http://www.ebi.ac.uk/pdbsum/5lab PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5lab" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5lab" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Matrix metalloproteinase 3D structures\|Matrix metalloproteinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Macrophage elastase]]		[[Category: Macrophage elastase]]
	[[Category: Calderone, V]]		[[Category: Calderone, V]]

OCA at 16:07, 10 August 2016

2016-08-10T16:07:27Z

← Older revision		Revision as of 16:07, 10 August 2016
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	The ~~entry 5lab~~ is ~~ON HOLD~~		==Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor NNGH==
			<StructureSection load='5lab' size='340' side='right' caption='[[5lab]], [[Resolution\|resolution]] 1.34Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5lab]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LAB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LAB FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NGH:N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL+HYDROXAMIC+ACID'>NGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lab OCA], [http://pdbe.org/5lab PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lab RCSB], [http://www.ebi.ac.uk/pdbsum/5lab PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lab ProSAT]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/MMP12_HUMAN MMP12_HUMAN]] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The structures of the catalytic domain of matrix metalloproteinase 12 in the presence of acetohydroxamic acid and N-isobutyl-N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid have been solved by x-ray diffraction in the crystalline state at 1.0 and 1.3-A resolution, respectively, and compared with the previously published x-ray structure at 1.2-A resolution of the adduct with batimastat. The structure of the N-isobutyl-N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid adduct has been solved by NMR in solution. The three x-ray structures and the solution structure are similar but not identical to one another, the differences being sizably higher in the loops. We propose that many of the loops show a dynamical behavior in solution on a variety of time scales. Different conformations of some flexible regions of the protein can be observed as "frozen" in different crystalline environments. The mobility in solution studied by NMR reveals conformational equilibria in accessible time scales, i.e., from 10(-5) s to ms and more. Averaging of some residual dipolar couplings is consistent with further motions down to 10(-9) s. Finally, local thermal motions of each frozen conformation in the crystalline state at 100 K correlate well with local motions on the picosecond time scale. Flexibility/conformational heterogeneity in crucial parts of the catalytic domain is a rule rather than an exception in matrix metalloproteinases, and its extent may be underestimated by inspection of one x-ray structure. Backbone flexibility may play a role in the difficulties encountered in the design of selective inhibitors, whereas it may be a requisite for substrate binding and broad substrate specificity.

	~~Authors~~: ~~Ravera~~, E., Calderone, V., Luchinat, C.		Conformational variability of matrix metalloproteinases: beyond a single 3D structure.,Bertini I, Calderone V, Cosenza M, Fragai M, Lee YM, Luchinat C, Mangani S, Terni B, Turano P Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5334-9. Epub 2005 Apr 4. PMID:15809432<ref>PMID:15809432</ref>

	~~Description: Crystal structure~~ of the ~~catalytic domain~~ of ~~human MMP12 complexed with the inhibitor NNGH~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased Structures~~]]		</div>
			<div class="pdbe-citations 5lab" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Macrophage elastase]]
	[[Category: Calderone, V]]		[[Category: Calderone, V]]
			[[Category: Luchinat, C]]
	[[Category: Ravera, E]]		[[Category: Ravera, E]]
	[[Category: ~~Luchinat, C~~]]		[[Category: Hydrolase]]
			[[Category: Hydrolase mmp-12]]

OCA: Protected "5lab" [edit=sysop:move=sysop]

2016-06-23T21:55:45Z

Protected "5lab" [edit=sysop:move=sysop]

← Older revision	Revision as of 21:55, 23 June 2016
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5lab is ON HOLD Authors: Ravera, E., Calderone, V., Luchinat, C. Description: Crystal structure of the catalytic domain of human MMP12 complexed wi...

2016-06-23T21:55:43Z

New page: '''Unreleased structure''' The entry 5lab is ON HOLD Authors: Ravera, E., Calderone, V., Luchinat, C. Description: Crystal structure of the catalytic domain of human MMP12 complexed wi...

New page

'''Unreleased structure'''

The entry 5lab is ON HOLD

Authors: Ravera, E., Calderone, V., Luchinat, C.

Description: Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor NNGH
[[Category: Unreleased Structures]]
[[Category: Calderone, V]]
[[Category: Ravera, E]]
[[Category: Luchinat, C]]